Fat-binding polymers

ABSTRACT

The present invention relates to a method for treating obesity, a method for reducing the absorption of dietary fat, and a method for treating hypertriglyceridemia in a patient and to particular polymers for use in the methods or in a manufacture of a medicament. The methods comprise the step of orally administering to a mammal, such as a human, a therapeutically effective amount of one or more fat-binding polymers. The administration of the fat-binding polymer of the invention facilitates the removal of fat from the body prior to digestion, with minimal side effects and low toxicity. In a preferred embodiment, the one or more fat-binding polymers are administered in combination with one or more lipase inhibitors, for example, lipstatin and tetrahydrolipstatin.

RELATED APPLICATIONS

This application is a Divisional of U.S. application Ser. No.09/353,329, filed Jul. 14, 1999, now U.S. Pat. No. 6,299,868, the entirecontents of which are hereby incorporated by reference.

BACKGROUND OF THE INVENTION

Human obesity is a recognized health problem with approximately 97million people considered clinically overweight in the United States.The accumulation or maintenance of body fat bears a direct relationshipto caloric intake. Therefore, one of the most common methods for weightcontrol to combat obesity is the use of relatively low-fat, low caloriediets, that is, diets containing less fat and calories than a “normaldiet” or that amount generally consumed by the patient.

The presence of fats in a great many food sources greatly limits thefood sources which can be used in a low-fat diet. Additionally, fatscontribute to the flavor, appearance and physical characteristics ofmany foodstuffs. As such, the acceptability of low-fat diets and themaintenance of such diets are difficult. Various chemical approacheshave been proposed for controlling obesity. Anorectic agents, such asdextroamphetamine, the combination of the non-amphetamine drugsphentermine and fenfluramine (“Phen-Fen”) and dexfenfluramine (Redux)alone, are associated with serious side effects. Indigestible materialssuch as OLESTRA™, mineral oil or neopentyl esters (see U.S. Pat. No.2,962,419) have been proposed as substitutes for dietary fat. Garciniaacid and derivatives thereof have been described as treating obesity byinterfering with fatty acid synthesis. Swellable crosslinked vinylpyridine resins have been described as appetite suppressants via themechanism of providing non-nutritive bulk, as in U.S. Pat. No.2,923,662. Surgical techniques, such as temporary ideal bypass surgery,are employed in extreme cases.

However, methods for treating obesity, such as those described above,have serious shortcomings with controlled diet remaining the mostprevalent technique for controlling obesity. As such, new methods fortreating obesity are needed.

SUMMARY OF THE INVENTION

The present invention relates to a method for treating obesity, a methodfor reducing the absorption of dietary fat, and a method for treatinghypertriglyceridemia in a patient and to particular polymers for use inthe methods or in a manufacture of a medicament. The methods comprisethe step of orally administering to a mammal, such as a human, atherapeutically effective amount of a fat-binding polymer. Theadministration of a fat-binding polymer of the invention facilitates theexcretion of fat from the body without digestion, with minimal sideeffects and low toxicity. In a preferred embodiment, the fat-bindingpolymers are administered in combination with a therapeuticallyeffective amount of a lipase inhibitor, such as the pancreatic lipaseinhibitors described in U.S. Pat. No. 4,598,089 to Hadvary et al. Thecombination administration can reduce undesirable side effects oftenencountered when lipase inhibitors, in particular, the pancreatic lipaseinhibitors lipstatin and tetrahydrolipstatin are administered alone. Forexample, a serious side effect resulting from the administration of alipase inhibitor is steatorrhea, or fatty stools.

The fat-binding polymers of the invention comprise at least onefat-binding region. A fat-binding region can include a region having apositive charge, a region which is hydrophobic or a region having apositive charge and which is hydrophobic.

In one embodiment, the fat-binding polymer is an aliphatic polymerselected from the group consisting of polyalkylacrylates,polyacrylamides, polyalkylmethacrylates, polymethacrylamides,poly-N-alkylacrylamides, poly-N-alkylmethacrylamides, substitutedderivatives thereof and copolymers thereof. For example, the substitutedderivatives of the polymers can be characterized by one or moresubstituents, such as substituted or unsubstituted, saturated orunsaturated alkyl, and substituted or unsubstituted aryl groups.Suitable substituents to employ on the alkyl or aryl groups include, butare not limited to, cationic or neutral groups, such as alkoxy, aryl,aryloxy, aralkyl, halogen, amine, and ammonium groups. For example, thepolymer can be poly(dimethylamino propylacrylamide),poly(trimethylammonium ethylacrylate), poly(trimethylammonium ethylmethacrylate), poly(trimethylammonium propyl acrylamide), poly(dodecylacrylate), poly(octadecyl acrylate), poly(octadecyl methacrylate) andcopolymers thereof.

In another embodiment, the fat binding polymer is a synthetic aminepolymer and pharmaceutically acceptable salts thereof. Amine polymers(or salts thereof) suitable for use in the invention include, but arenot limited to, substitued or unsubstituted polymers or copolymers ofthe following monomers: allylamine, diallyldimethyl ammonium,ethyleneimine, vinylamine, diallylamine, vinylimidazole anddiallylmethylamine.

In another embodiment, the fat binding polymer is an amine derivative ofan anhydride containing polymer.

In yet another embodiment, the fat-binding polymer is ahydroxyl-containing polymer, for example, poly(vinylalcohol).

In a specific embodiment, the fat-binding polymer is an amine-containingpolymer wherein one or more hydrophobic regions are bound to a portionof the amine nitrogens of the amine polymer. In a particular embodiment,between about 1 and about 60 percent of the amine nitrogens aresubstituted, preferably between about 1 and about 30 percent.

In another embodiment, the hydrophobic region of the fat-binding polymercan include a hydrophobic moiety, for example, a substituted orunsubstituted, normal, branched or cyclic alkyl group having at leastfour carbons. In a particular embodiment, the hydrophobic moiety is analkyl group of between about four and thirty carbons.

In another embodiment, the hydrophobic region is a quaternaryamine-containing moiety having a terminal hydrophobic substituent.Suitable hydrophobic regions which can include a hydrophobic moietyand/or a quaternary amine-containing moiety are described herein and inU.S. Pat. Nos. 5,607,669, 5,679,717 and 5,618,530, the entire contentsof which are incorporated herein by reference in their entirety.

The polymers of the present invention offer desirable pharmacologicalproperties such as excellent fat binding properties and low toxicity. Inaddition, when the fat-binding polymers are administered in combinationwith lipase inhibitors, as described herein, undesirable side effectsexperienced, such as steatorrhea, when the lipase inhibitors areadministered alone can be lessened.

DETAILED DESCRIPTION OF THE INVENTION

The features and other details of the invention will now be moreparticularly described and pointed out below as well as in the claims.It will be understood that the particular embodiments of the inventionare shown by way of illustration and not as limitations of theinvention. The principle features of this invention can be employed invarious embodiments without departing from the scope of the invention.

In one aspect, the invention relates to a method for treating obesitycomprising the step of orally administering to a mammal atherapeutically effective amount of one or more fat-binding polymers. Ina preferred embodiment, the fat-binding polymer is administered incombination with a therapeutically effective amount of a lipaseinhibitor.

In another aspect, the invention relates to a method for reducing theabsorption of dietary fat comprising the step of orally administering toa mammal a therapeutically effective amount of one or more fat-bindingpolymers. In a preferred embodiment, the fat-binding polymer isadministered in combination with a therapeutically effective amount of alipase inhibitor.

In yet another aspect, the invention relates to a method for treatinghypertriglyceridemia in a mammal comprising the step of orallyadministering to a mammal a therapeutically effective amount of one ormore fat-binding polymers. In a preferred embodiment, the fat-bindingpolymer is administered in combination with a therapeutically effectiveamount of a lipase inhibitor.

A particular aspect of the invention relates to a method for treatingsteatorrhea comprising the step of orally administering to a mammal atherapeutically effective amount of a fat-binding polymer. In a specificembodiment, the steatorrhea is a result of the administration of alipase inhibitor.

The invention also relates to fat-binding polymers useful in the methodof the invention.

“Lipases” as that term is used herein, are ubiquitous enzymes whichhydrolyze ester bonds in neutral lipids. Examples of lipases include,but are not limited to, pancreatic and gastric lipases. The preferredsubstrates of lipases are insoluble in water. Lipases exhibit maximalactivity in the presence of lipid/water interfaces. For example,pancreatic lipase, which is the key enzyme of dietary triglycerideabsorption, exerts it activity at the water/lipid interface, inconjunction with bile salts and co-lipase.

“Lipase inhibitor” as that term is used herein refers to compounds whichare capable of inhibiting the action of lipases, for example, gastricand pancreatic lipases. Lipstatin and its tetrahydro derivative,Tetrahydrolipstatin, as described in U.S. Pat. No. 4,598,089 to Hadvaryet al., the entire content of which is hereby incorporated by reference,are potent inhibitors of both gastric and pancreatic lipases, as well ascholesterol ester hydrolase. Lipstatin is a natural product of microbialorigin, and tetrahydrolipstatin is the result of catalytic hydrogenationof lipstatin. Other lipase inhibitors include a class of compoundcommonly referred to as Panclicins. Panclicins are analogues ofTetrahydrolipstatin (See e.g., Mutoh, M., et al., “Panclicins, NovelPancreatic Lipase Inhibitors, II. Structural Elucidation,” The Journalof Antibiotics, 47(12): 1376-1384 (1994), the entire content of which ishereby incorporated by reference.)

“Fat-binding polymers”, as that term is used herein, are polymers whichabsorb, bind or otherwise associate with fat thereby inhibiting(partially or completely) fat digestion, hydrolysis, or absorption inthe gastrointestinal tract and/or facilitate the removal of fat from thebody prior to digestion. The fat-binding polymers comprise one or morefat-binding regions. “Fat-binding regions”, as defined herein caninclude a positively charged region, a hydrophobic region, or a regionwhich is both positively charged and hydrophobic.

“Fats”, as that term is used herein, are solids or liquid oils generallyconsisting of glycerol esters of fatty acids. Sources of fats includeboth animal and vegetable fats, for example, triglyceride esters ofsaturated and/or unsaturated fatty acids, free fatty acids,diglycerides, monoglycerides, phospholipids and cholesterol esters arefats, as defined herein.

A variety of polymers can be employed in the invention described herein.The polymers are synthetic polymers which can be aliphatic, or aromatic.However, aliphatic and synthetic polymers are preferred. A “syntheticpolymer”, as that term is employed herein, is a polymer which is notobtainable from a natural source either directly or through a minorderivatization of the naturally occurring form. Further, the polymer canbe hydrophobic, hydrophilic or copolymers of hydrophobic and/orhydrophilic monomers. Particularly preferred polymers comprise monomershaving both cationic and hydroxy functional groups, and/or comprise acombination of separate monomers each having either a cationic orhydroxy functional group. Other preferred polymers comprise monomershaving both cationic and hydrophobic groups, and/or comprise acombination of separate monomers each having either a cationic or ahydrophobic functional groups. As used herein the term “combination ofmonomers” or “combination of repeat units” means that at least one ofeach monomer or at least one of each repeat unit are present in theresulting polymerized polymer in any order. Many polymers can beconveniently manufactured from olefinic or ethylenic monomers (such asvinylalcohol, allylamine or acrylic acid) or condensation polymers.Examples of the preparation of preferred polymers of the invention areincluded in Examples 1-98.

For example, the polymers can include substituted or unsubstitutedpolyvinylalcohol, polyvinylamine, poly-N-alkylvinylamine,polyallylamine, poly-N-alkylallylamine, polydiallylamine,poly-N-alkyldiallylamine, polyalkylenimine, other polyamines,polyethers, polyamides, polyacrylic acids, polyalkylacrylates,polyacrylamides, polymethacrylic acids, polyalkylmethacrylates,polymethacrylamides, poly-N-alkylacrylamides,poly-N-alkylmethacrylamides, polystyrene, polyvinylnaphthalene,polyethylvinylbenzene, polyaminostyrene, polyvinylbiphenyl,polyvinylanisole, polyvinylimidazolyl, polyvinylpyridinyl,polydimethylaminomethylstyrene, polydiallylmethylammonium chloride,polytrimethylammonium ethyl methacrylate, polytrimethylammonium ethylacrylate, and copolymers thereof. In addition, the polymers can befurther characterized by one or more substituents such as substitutedand unsubstituted, saturated or unsaturated alkyl, and substituted orunsubstituted aryl groups. Suitable groups to employ include cationic orneutral groups, such as alkoxy, aryl, aryloxy, aralkyl, halogen, amine,ammonium groups, substituted or unsubstituted oxypolyethylene oxide, andmono, di or higher hydroxyalkyl groups.

Particularly preferred polymers (or salts thereof) include substitutedor unsubstituted polydiethylammonium chloride, polyvinylimidazole,polyalkylacrylates, polyacrylamides, polyalkylmethacrylates,polymethacrylamides, poly-N-alkylacrylamides,poly-N-alkylmethacrylamides and copolymers thereof. These polymers canbe further characterized by one or more substituents such as thosediscussed above.

Other particularly preferred polymers include aliphatic amine polymers,such as polyallylamine, polydiallylamine, polydiallylmethylamine,polyvinylamine, polyethylenimine. In a specific embodiment, the aminepolymer comprises one or more hydrophobic regions which are bound to aportion of the amine nitrogens of the amine polymer. In a particularembodiment, between about 1 and about 60 percent of the amine nitrogensare substituted, preferably between about 1 and about 30 percent.

Additional particularly preferred polymers include maleic anhydride andmaleic anhydride olefinic copolymers, itaconic anhydride, and aminederivatives thereof. The amine derivatives may preferably containdimethyl amino groups.

In one embodiment, the hydrophobic region of the fat-binding polymer caninclude a hydrophobic moiety, for example, a substituted orunsubstituted, normal, branched or cyclic alkyl group having at leastfour carbons. In a specific embodiment, the hydrophobic moiety is analkyl group of between about four and thirty carbons.

In another embodiment, the hydrophobic region is a quaternaryamine-containing moiety having a terminal hydrophobic substituent.

In yet another embodiment, the fat-binding region comprises a nitrogen,for example, the nitrogen of an amine, capable of possessing a positivecharge under conditions present in the gastro-intestinal tract. Forexample, a quaternary amine-containing moiety, or the nitrogen of apolyamine.

In yet another embodiment, the fat-binding polymer is ahydroxyl-containing polymer, for example, poly(vinylalcohol) which cancomprise further fat-binding regions. For example, the polymer comprisesa repeat unit having the formula

wherein R is a hydrophobic region.

Preferred polymers are copolymers that comprise both cationic monomerssuch as those containing nitrogen, and monomers with hydroxy groups.

Other polymers and methods of preparation, which can be used in theclaimed invention have been reported in the patent literature in, forexample, U.S. Pat. Nos. 5,487,888, 5,496,545, 5,607,669, 5,618,530,5,624,963, 5,667,775, and 5,679,717 and co-pending U.S. Applicationshaving Ser. Nos. 08/471,747, 08/482,969, 08/567,933, 08/659,264,08/823,699, 08/835,857, 08/470,940, 08/461,298, 08/826,197, 08/777,408,08/927,247, 08/964,956, 08/964,498, and 08/964,536, the entire contentsof all of which are incorporated herein by reference.

The polymer can be linear or crosslinked. Crosslinking can be performedby reacting the copolymer with one or more crosslinking agents havingtwo or more functional groups, such as electrophilic groups, which reactwith, for example, amine groups to form a covalent bond. Crosslinking inthis case can occur, for example, via nucleophilic attack of the polymeramino groups on the electrophilic groups. This results in the formationof a bridging unit which links two or more amino nitrogen atoms fromdifferent polymer strands. Suitable crosslinking agents of this typeinclude compounds having two or more groups selected from among acylchloride, epoxide, and alkyl-X, wherein X is a suitable leaving group,such as a halo, tosyl or mesyl group. Examples of such compoundsinclude, but are not limited to, epichlorohydrin, succinyl dichloride,acryloyl chloride, butanedioldiglycidyl ether, ethanedioldiglycidylether, pyromellitic dianhydride, and dihaloalkanes. These crosslinkingagents are referred to herein as multifunctional crosslinking agents.

The polymer composition can also be crosslinked by including amultifunctional co-monomer as the crosslinking agent in thepolymerization reaction mixture. A multifunctional co-monomer can beincorporated into two or more growing polymer chains, therebycrosslinking the chains. Suitable multifunctional co-monomers include,but are not limited to, diacrylates, triacrylates, and tetraacrylates,dimethacrylates, diacrylamides, and dimethacrylamides. Specific examplesinclude ethylene glycol diacrylate, propylene glycol diacrylate,butylene glycol diacrylate, ethylene glycol dimethacrylate, butyleneglycol dimethacrylate, methylene bis(methacrylamide), ethylenebis(acrylamide), ethylene bis(methacrylamide), ethylidenebis(acrylamide), ethylidene bis(methacrylamide), pentaerythritoltetraacrylate, trimethylolpropane triacrylate, bisphenol Adimethacrylate, and bisphenol A diacrylate. Other suitablemultifunctional monomers include polyvinylarenes, such asdivinylbenzene.

The amount of cross-linking agent is typically between about 0.01 andabout 10 weight % based on the combined weight of crosslinking agent andmonomers, with 0.1-3% being preferred. Typically, the amount ofcross-linking agent that is reacted with the polymer, when thecrosslinking agent is a multifunctional agent, is sufficient to causebetween about 0.1 and 6 percent of the nucleophiles present on themonomer, for example, an amine to react with the crosslinking agent.

The hydrophobic region or regions of the fat-binding polymers includebut are not limited to, for example, a hydrophobic moiety such as asubstituted or unsubstituted, normal, branched or cyclic alkyl grouphaving at least about four carbons and preferably at least 6 carbons.For example, a hydrophobic moiety such as an alkyl group of at leastfour carbons and preferably at least 6 carbons can be bound to thefat-binding polymer, for example, through an amine of the fat-bindingpolymer.

A “hydrophobic moiety (group)”, as the term is used herein, is a moietywhich, as a separate entity, is more soluble in octanol than water. Forexample, the octyl group (C₈H₁₇) is hydrophobic because its parentalkane, octane, has greater solubility in octanol than in water. Thehydrophobic moieties can be a saturated or unsaturated, substituted orunsubstituted hydrocarbon group. Such groups include substituted andunsubstituted, normal, branched or cyclic alkyl groups having at leastfour carbon atoms, substituted or unsubstituted arylalkyl orheteroarylalkyl groups and substituted or unsubstituted aryl orheteroaryl groups. Preferably, the hydrophobic moiety includes an alkylgroup of between about four and thirty carbons. Specific examples ofsuitable hydrophobic moieties include the following alkyl groupsn-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl,n-tetradecyl, n-octadecyl, 2-ethylhexyl, 3-propyl-6-methyl decyl, phenyland combinations thereof. Other examples of suitable hydrophobicmoieties include haloalkyl groups of at least six carbons (e.g.,10-halodecyl), hydroxyalkyl groups of at least six carbons (e.g.,11-hydroxyundecyl), and aralkyl groups (e.g., benzyl).

The positively charged region or regions of the fat binding polymers mayinclude primary, secondary, tertiary or quaternary amines. Optionally,the positively charged region or regions of the fat-binding polymers mayinclude an amine nitrogen capable of possessing a positive charge underconditions present in the gastro-intestinal tract and a quaternaryamine-containing moiety. Suitable quaternary amine-containing moietiesused in conjunction with acrylate or acrylamide polymers, for example,include alkyl trialkylammonium groups also referred to as ammonioalkylgroups. The term, “ammonioalkyl”, as used herein, refers to an alkylgroup which is substituted by a nitrogen bearing three additionalsubstituents. Thus, the nitrogen atom is an ammonium nitrogen atom whichbears an alkylene substituent, which links the ammonium nitrogen atom tothe polymer, and three additional terminal alkyl substituents havingfrom about one to about twenty-four carbons. A “terminal substituent” ofthe quaternary amine-containing moiety, as the term is employed herein,is any one of the three substituents on the quaternary amine nitrogen.In a specific embodiment, the polymer is an amine polymer and thealkylene group links the ammonium nitrogen atom to the nitrogen atom ofthe polymer. It is to be understood that multiple moieties can be boundto the same amine and/or different amines of the polymer composition.

In another embodiment, the quaternary amine-containing moiety can bearat least one terminal hydrophobic alkyl substituent, such as an alkylgroup having between about four and twenty-four carbons, therebyproviding both a hydrophobic region and a positively charged region incombination.

An ammonioalkyl group will further include a negatively chargedcounterion, such as a conjugate base of a pharmaceutically acceptableacid. Examples of suitable counterions include Cl⁻, PO₄ ⁻, Br⁻, CH₃SO₃⁻, HSO₄ ⁻, SO₄ ²⁻, HCO₃ ⁻, CO₃ ²⁻, acetate, lactate, succinate,propionate, butyrate, ascorbate, citrate, maleate, folate, tartrate,polyacrylate, an amino acid derivative, and a nucleotide.

Suitable ammonioalkyl groups are of the general formula:

wherein, R¹, R² and R³ represent an alkyl group, wherein each R¹-R³,independently, is a normal or branched, substituted or unsubstitutedalkyl group having a carbon atom chain length of between about one toabout twenty-four carbon atoms, n is an integer having a value of two ormore and Y is a negatively charged counterion. In a particularembodiment, R¹, R² and R³ are all methyl groups and n is an integerbetween about 2 and about 12. Examples of preferred alkylene linkinggroups are ethyl, propyl, butyl, pentyl, hexyl, octyl, and decyl groups.Example of suitable quaternary amine-containing moieties include, butare not limited to:

3-(trimethylammonio)propyl;

4-(trimethylammonio)butyl;

6-(trimethylammonio)hexyl;

8-(trimethylammonio)octyl;

10-(trimethylammonio)decyl;

12-(trimethylammonio)dodecyl and combinations thereof. A particularlypreferred amine-containing moiety is a 6-(trimethylammonio)hexyl group.

Alternatively, a quaternary amine-containing moiety and a hydrophobicmoiety are present in the same substituent, thereby providing both apositively charged and hydrophobic region in combination. For example,the quaternary amine nitrogen or ammonium nitrogen of the quaternaryamine-containing moiety is bound to the polymer backbone by an alkylenehaving two or more carbons. However, at least one of the three terminalsubstituents (R¹, R² and R³) of the ammonium nitrogen is a hydrophobicalkyl group having from four to about twenty-four carbons. The remainingterminal substituents are each independently a normal or branched,substituted or unsubstituted alkyl group having from one to abouttwenty-four carbons or a hydrogen atom. In another embodiment, at leasttwo of the three terminal substituents can be hydrophobic alkyl groupshaving from four to about twenty-four carbons, the remainder having fromone to about twenty-four carbons or a hydrogen atom. In a furtherembodiment, all three of the terminal substituents can be hydrophobicalkyl groups having from six to about twenty-four carbons.

A “hydrophobic alkyl group”, as that term is employed herein, includes asubstituted or unsubstituted alkyl group having from four to abouttwenty-four carbons and which is hydrophobic, as earlier defined. Thehydrophobic alkyl group can be, for example, a normal or branched,substituted or unsubstituted alkyl group having from six to abouttwenty-four carbons.

Particular examples of quaternary amine-containing moieties, whichprovide both a hydrophobic and quaternary amine-containing substituent,include, but are not limited to:

4-(dioctylmethylammonio)butyl;

3-(dodecyldimethylammonio)propyl;

3-(octyldimethylammonio)propyl;

3-(decyldimethylammonio)propyl;

5-(dodecyldimethylammonio)pentyl;

6-(dimethyldecylammonio)hexyl;

6-(decyldimethylammonio)hexyl;

3-(tridecylammonio)propyl;

3-(docosyldimethylammonio)propyl;

6-(docosyldimethylammonio)hexyl;

4-(dodecyldimethylammonio)butyl;

3-(octadecyldimethylammmonio)propyl;

3-(hexyldimethylammonio)propyl;

3-(methyldioctylammonio)propyl;

3-(didecylmethylammonio)propyl;

3-(heptyldimethylammonio)propyl;

3-(dimethylnonylammonio)propyl;

6-(dimethylundecylammonio)hexyl;

4-(heptyldimethylammonio)butyl;

4-(dioctylmethylammonio)butyl;

6-(octyldimethylammonio)hexyl;

12-(decyldimethylammonio)dodecyl;

3-(dimethylundecylammonio)propyl; and

3-(tetradecyldimethylammonio)propyl.

Other suitable quaternary amine-containing moieties include secondaryand tertiary analogs, such as 4-(dioctylmethylammonio)4-methylbutyl and4-(dioctylmethylammonio)-4,4-dimethylbutyl.

The fat-binding polymers of the invention can be formed, for example, byreacting a polymer, which can be linear or crosslinked, with a suitablealkylating agent or by polymerizing an alkylated monomer.

An “alkylating agent”, as that term is employed herein, means a reactantthat, when reacted with a monomer or a copolymer characterized by arepeat unit of the invention and having a nucleophilic site capable ofreaction with the alkylating agent, causes a hydrophobic substituent, asdescribed herein, to be covalently bound to one or more of sites on thefat-binding polymer, for example, the amine nitrogen atoms or hydroxyloxygens of an amine-containing or hydroxyl-containing monomer orpolymer, respectively. Further, when multiple substituents are employed,they can be bound to the same and/or different nucleophilic sites of thefat-binding polymer, for example, the same and/or different aminenitrogens of an amine-containing fat-binding polymer or hydroxyl oxygenof a hydroxyl-containing polymer.

Suitable alkylating agents are compounds comprising an alkyl group oralkyl derivative, having at least four carbon atoms, which is bonded toa leaving group such as a halo (e.g., chloro, bromo or iodo), tosylate,mesylate or epoxy group).

Examples of suitable alkylating agents which provide a hydrophobicmoiety include alkyl halides having at least four carbon atoms, such asn-hexyl halide, n-heptyl halide, n-octyl halide, n-nonyl halide, n-decylhalide, n-undecyl halide, n-dodecyl halide, n-tetradecyl halide,n-octadecyl halide, and combinations thereof. Other examples include: adihaloalkane that includes an alkyl group of at least four carbons(e.g., a 1,10-dihalodecane); a hydroxyalkyl halide having at least fourcarbon atoms (e.g., an 11-halo-1-undecanol); an aralkyl halide (e.g., abenzyl halide); an alkyl epoxy ammonium salt having at least six carbons(e.g., glycidylpropyl-trimethylammonium salts) and epoxyalkylamideshaving at least six carbons (e.g., N-(2,3-epoxypropyl)butylamine orN-(2,3-epoxypropyl)hexanamide). Preferred halogen components of thealkyl halides are bromine and chlorine. Particularly preferredalkylating agents which, when reacted with the polymer composition, willcause formation of an amine polymer reaction product that includes afirst substituent, are 1-bromodecane and 1-chlorooctane.

Examples of suitable alkylating agents which can provide a quaternaryamine-containing moiety have the general formula:

wherein,

R¹, R², and R³ represent an alkyl group, wherein each R independently isa normal or branched, substituted or unsubstituted alkyl group having acarbon atom chain length of between about one to about twenty fourcarbon atoms,

n is an integer having a value of two or more,

X is a leaving group as earlier described, and

Y is a negatively charged counterion.

When at least one of the three terminal substituents of the quaternaryamine alkylating agent is a hydrophobic alkyl group having from four toabout twenty-four carbons, the alkylating agent therefore provides botha hydrophobic moiety and a quaternary amine-containing moiety. Thealkylene group in this instance is three or more carbon atoms in length.

Particular examples of quaternary ammonium compounds suitable asalkylating agents include the following:

(4-bromobutyl)dioctylmethylammonium bromide;

(3-bromopropyl)dodecyldimethylammonium bromide;

(3-chloropropyl)dodecyldimethylammonium bromide;

(3-chloropropyl)decyldimethylammonium bromide;

(5-tosylpentyl)dodecyldimethylammonium bromide;

(6-bromohexyl)dimethyldecylammonium bromide;

(12-bromododecyl)decyldimethylammonium bromide;

(3-bromopropyl)tridecylammonium bromide;

(3-bromopropyl)docosyldimethylammonium bromide;

(6-bromohexyl)docosyldimethylammonium bromide;

(4-chlorobutyl)dodecyldimethylammonium bromide;

(3-chloropropyl)octadecyldimethylammonium bromide;

(3-bromopropyl)octyldimethylammonium bromide;

(4-iodobutyl)dioctylmethylammonium bromide;

(2,3-epoxy propyl)decyldimethylammonium bromide; and

(6-bromohexyl)docosyldimethyammonium bromide.

Other suitable alkylating agents include secondary and tertiary analogs,such as (3-bromobutyl)dioctylmethylammonium bromide and(3-chloro-3,3-dimethyl propyl)dioctylmethylammonium bromide.

Examples of suitable alkyl trimethylammonium alkylating agents includealkyl halide trimethylammonium salts, such as:

(4-halobutyl)trimethylammonium salt;

(5-halopentyl)trimethylammonium salt;

(6-halohexyl)trimethylammonium salt;

(7-haloheptyl)trimethylammonium salt;

(8-halooctyl)trimethylammonium salt;

(9-halononyl)trimethylammonium salt;

(10-halodecyl)trimethylammonium salt;

(11-haloundecyl)trimethylammonium salt;

(12-halododecyl)trimethylammonium salt; and combinations thereof Aparticularly preferred quaternary amine-containing alkylating agent is(6-bromohexyl)-trimethylammonium bromide.

The fat-binding polymers of the invention can be formed, for example, byreacting a polymer, which can be linear or crosslinked, with a suitablemodifying agent. A “modifying agent”, as that term is employed herein,means a reactant that, when reacted with a monomer or a copolymercharacterized by a repeat unit of the invention and having anucleophilic site capable of reaction with the modifying agent, causes ahydrophobic substituent, as described herein, to be covalently bound toone or more of sites on the fat-binding polymer, for example, the aminenitrogen atoms of an amine-containing polymer. Further, when multiplesubstituents are employed, they can be bound to the same and/ordifferent nucleophilic sites of the fat-binding polymer, for example,the same and/or different amine nitrogens of an amine-containingfat-binding polymer.

Suitable modifying agents are compounds comprising substituted alkylgroup or alkyl aromatic groups which is bonded to a leaving group suchas a halo (e.g., chloro, bromo or iodo), tosylate, mesylate or epoxygroup). Examples of suitable modifying agents which provide ahydrophilic moiety include haloalkanols, (for example, 2-bromoethanol,3-bromopropanol, 4-bromobutanol, 4-chlorobutanol and 3-bromo-2-hydroxypropanol), haloalkanoic acids (for example chloroacetic acid,bromoacetic acid, 3-bromo propionic acid and 4-bromobutyric acid,glycidol, glycidyl trimethylammonium chloride, and ethylene oxide.Particularly preferred modifying agents which include glycidol, and2-bromoethanol.

Preferred fat binding polymers, copolymers or salts thereof inaccordance with the invention are described in Examples 1-98.

Even more preferred fat binding polymers, copolymers (and/or saltsthereof) of the invention comprises at least one repeat unit or acombination of repeat units selected from the following group of repeatunit formulas, or combinations of repeat unit formulas.

Particularly preferred fat binding polymers, copolymers (and/or saltsthereof) of the invention comprise the following:

A polymer of Formula II wherein: R1=H, R2=H, R5=CH_(3,) m=1, p=about 114and wherein the resulting polymer may be expressed asPoly((3-acrylamidopropyl)trimethylammoniumchloride-co-O-acryloyl-O′-methylpolyethyleneglycol 5000). Preferably,such polymer contains 11 wt % of the PEG-containing monomer;

A polymer of Formula III wherein R1=H, R2=H, R4=C₁₂H₂₅, R5=CH₃ andwherein the resulting polymer may be expressed asPoly(3-methyl-1-vinylimidazolium chloride-co-acrylamide-co-dodecylacrylamide). Even more preferably, such polymer has a monomer mole ratioof 35/70/5;

A polymer of Formula IV wherein R1=H, R2=H, R3=H, R4=C₆H₅(phenyl),m=1and wherein the resulting polymer may be expressed asPoly((3-acrylamidopropyl)trimethylammoniumchloride-co-acrylamide-co-N-phenylacrylamide). Even more preferably,such polymer has a Mol % monomer composition of 25/70/5;

A polymer of Formula V wherein R1=H, R2=H, R3=H, R4=C₁₈H₃₇,R5=CH_(3,)m=1 and wherein the resulting polymer may be expressed asPoly((3-acrylamidopropyl)trimethylammoniumchloride-co-acrylamide-co-N-methyl-N-octadecylacrylamide). Even morepreferably such polymer has a Mol % monomer composition of 25/70/5;

The polymer of Formula VI which may be expressed asPoly(N,N-diallyl-N,N-di(2,3-dihydroxypropyl)ammonium chloride);

The polymer of Formula VII wherein R5=methyl and wherein such polymermay be expressed asPoly(N,N-diallyl-N-methyl-N-(2,3-dihydroxypropyl)ammonium chloride);

The polymer of Formula VIII which may be expressed asPoly(N,N-di(2,3-dihydroxypropyl)allylamine)hydrochloride;

A polymer of Formula IX wherein, R5=H, R6=H, R7=CH_(3,) R8=CH₃ andwherein such polymer may be expressed asPoly(N-(3-dimethylaminopropyl)maleimide-co-ethylene)hydrochloride;

A Polymer of Formula X wherein R5=H, R6=CH_(3,) X=tartrate, and whereinsuch polymer may be expressed asPoly(N-methyl-N,N-diallylammonium)tartrate.

In addition, another particularly preferred polymer of the invention maybe expressed as Polyethyleneimine 80% ethoxylated, the structure ofwhich is understood in the art. Exemplative synthetic schemes for eachof the preferred and particularly preferred polymers of the inventionmay be found in the Examples and particularly in Examples.

In another embodiment, the fat-binding polymer can have a lipaseinhibitor covalently bound to the polymer as described inPCT/US99/00195. In a further embodiment, the fat-binding polymer can beadministered in combination with a lipase inhibitor which is covalentlybound to a polymer as described in PCT/US99/00195, the entire content ofwhich is incorporated herein by reference.

As used herein, the terms “therapeutically effective amount” and“therapeutic amount” are synonymous. The terms refer to an amount whichis sufficient to treat obesity, reduce the absorption of fat or treathypertriglyceridemia. The dosage of fat-binding polymer administered tothe patient will vary depending among other things on the weight of thepatient and the general health of the patient. The dosage can bedetermined with regard to established medical practice. The amount offat-binding polymer administered can be in the range of from about 0.01mg/kg of body weight/day to about 1 g/kg of body weight/day. The amountof lipase inhibitor which can be administered in combination with thefat-binding polymers of the invention can be determined with regard toaccepted medical practice (e.g. the Physicians Desk Reference).

As disclosed above, in a preferred embodiment, the preferred andparticularly preferred fat-binding polymers in accordance with theinvention are administered in combination with a lipase inhibitor, asdescribed herein. The term “in combination” in this context includesboth simultaneous or sequential administration (either type of compoundfirst) of the fat-binding polymer and lipase inhibitor. The fat-bindingpolymer and lipase inhibitor, when used in combination, can be employedtogether in the same dosage form or in separate dosage forms taken atthe same time or within a time period, wherein both the fat-bindingpolymer and lipase inhibitor are present in a therapeutically effectiveamount.

The fat-binding polymers of the invention can be formulated usingconventional inert pharmaceutical adjuvant materials into dosage formswhich are suitable for oral administration. The oral dosage formsinclude tablets, capsules, suspension, solutions, and the like. Theidentity of the inert adjuvant materials which are used in formulatingthe fat-binding polymers of the invention will be immediately apparentto persons skilled in the art. These adjuvant materials, eitherinorganic or organic in nature, include, for example, gelatin, albumin,lactose, starch, magnesium stearate, preservatives (stabilizers),melting agents, emulsifying agents, salts, and buffers.

In patients with hypertriglyceridemia it is to be understood that thepatient does not necessarily suffer from hypercholesterolemia.

EXAMPLES Example 1

Poly((3-acrylamidopropyl)trimethylammoniumchloride-co-acrylamide-co-N-decylacrylamide) Mol % monomer composition:25/70/5

A 250-mL round-bottomed flask was fitted with an overhead stirrer, areflux condenser, and a thermocouple probe. The following materials wereplaced into the flask in the order specified: a solution ofdecylacrylamide (2.83 g, 0.0134 mole) in tert-butanol (45 mL),3-acrylamidopropyltrimethylammonium chloride (18.45 g of a 75 percentsolution in water, 0.067 mole), deionized water (40 mL), and acrylamide(13.33 g, 0.1875 mole). The resulting mixture was stirred and heated to50° C. A clear, slightly yellow solution resulted. The solution wassparged for at least 30 minutes with a vigorous nitrogen flow from an18-gauge syringe needle whose tip was placed below the surface of thestirring solution. The radical initiator2,2′azobis(2-amidinopropane)dihydrochloride (0.363 g, 0.00134 mole) wasthen added to the solution and the temperature was increased to 60° C.The solution was stirred at 60° C. for 14-16 hours. The solution wasthen cooled to room temperature and poured into 3 L of isopropanol,resulting in precipitation of the polymeric product as a colorlesssolid. This mixture was stirred for 1-3 hours, and the isopropanol wasdecanted away from the polymer product. A fresh 3-L portion ofisopropanol was then added, and the mixture was stirred for 3-6 hours.Again, the isopropanol was decanted away, and another 3-L portion offresh isopropanol was added to the polymer. The mixture was stirred for6-14 hours and the isopropanol was decanted away from the polymerproduct. The polymer was placed on a glass tray, and dried in aforced-air oven at 70° C. for 24-48 hours. The dried solid was thenground to a fine powder using a commercial coffee grinder. The finepowder was placed into a glass tray in a forced air oven at 70° C. forat least 24 hours. A colorless solid (30.04 g) was obtained.

Example 2

Poly((3-acrylamidopropyl)trimethylammoniumchloride-co-acrylamide-co-N-decylacrylamide) Mol % monomer composition:25/65/10

The procedure of example 1 was followed substituting the followingmaterials and amounts: decylacrylamide (5.33 g, 0.0252 mole),3-acrylamidopropyltrimethylammonium chloride (17.37 g of a 75 percentsolution in water, 0.063 mole), deionized water (40.5 mL), acrylamide(11.65 g, 0.1638 mole), 2,2′azobis(2-amidinopropane)dihydrochloride(0.342 g, 0.00126 mole). The amount of polymer obtained was 30.7 g.

Example 3

Poly((3-acrylamidopropyl)trimethylammoniumchloride-co-acrylamide-co-N-decylacrylamide) Mol % monomer composition:25/60/15

The procedure of example 1 was followed substituting the followingmaterials and amounts: decylacrylamide (7.55 g, 0.0357 mole),3-acrylamidopropyltrimethylammonium chloride (16.4 g of a 75 percentsolution in water, 0.060 mole), deionized water (41 mL), acrylamide(10.15 g, 0.1428 mole), 2,2′azobis(2-amidinopropane)dihydrochloride(0.332 g, 0.00119 mole). The amount of polymer obtained was 25.6 g.

Example 4

Poly((3-acrylamidopropyl)trimethylammoniumchloride-co-acrylamide-co-N,N-didecylacrylamide) Mol % monomercomposition: 25/70/5

The procedure of example 1 was followed substituting the followingmaterials and amounts: didecylacrylamide (3.69 g, 0.0105 mole) intert-butanol (37 mL), 3-acrylamidopropyltrimethylammonium chloride(14.48 g of a 75 percent solution in water, 0.053 mole), deionized water(34.4 mL), acrylamide (10.15 g, 0.147 mole),2,2′azobis(2-amidinopropane)dihydrochloride (0.285 g, 0.00105 mole). Theamount of polymer obtained was 23.62 g.

Example 5

Poly((3-acrylamidopropyl)trimethylammoniumchloride-co-acrylamide-co-N-phenylacrylamide) Mol % monomer composition:75/20/5

The procedure of example 1 was followed substituting the followingmaterials and amounts: phenylacrylamide (1.04 g, 0.0071 mole) intert-butanol (37.5 mL), 3-acrylamidopropyltrimethylammonium chloride(29.27 g of a 75 percent solution in water, 0.106 mole), deionized water(30 mL), acrylamide (2.01 g, 0.028 mole),2,2′azobis(2-amidinopropane)dihydrochloride (0.192 g, 0.00071 mole). Theamount of polymer obtained was 26.1 g.

Example 6

Poly((3-acrylamidopropyl)trimethylammoniumchloride-co-acrylamide-co-N-benzylacrylamide) Mol % monomer composition:75/20/5

The procedure of example 1 was followed substituting the followingmaterials and amounts: benzylacrylamide (0.91 g, 0.0056 mole) intert-butanol (51 mL), 3-acrylamidopropyltrimethylammonium chloride(23.32 g of a 75 percent solution in water, 0.085 mole), deionized water(40 mL), acrylamide (1.60 g, 0.023 mole),2,2′azobis(2-amidinopropane)dihydrochloride (0.192 g, 0.00056 mole). Theamount of polymer obtained was 17.8 g.

Example 7

Poly((3-acrylamidopropyl)trimethylammoniumchloride-co-N-tert-octylacrylamide) Mol % monomer composition: 90/10

The procedure of example 1 was followed using the following reagents:N-tert-octylacrylamide (2.24 g, 0.0122 mole) in tert-butanol (50 g),3-acrylamidopropyltrimethylammonium chloride (30.25 g of a 75 percentsolution in water, 0.110 mole), deionized water (50 mL),2,2′azobis(2-amidinopropane)dihydrochloride (0.166 g, 0.00061 mole). Theamount of polymer obtained was 21.2 g.

Example 8

Poly((3-acrylamidopropyl)trimethylammoniumchloride-co-N-butylacrylamide) Mol % monomer composition: 25/75

The procedure of example 1 was followed using the following reagents:N-butylacrylamide (5.06 g, 0.04 mole) in tert-butanol (13.38 g),3-acrylamidopropyltrimethylammonium chloride (3.65 g of a 75 percentsolution in water, 0.013 mole), deionized water (8.9 mL),2,2′azobis(2-amidinopropane)dihydrochloride (0.072 g, 0.00027 mole). Theamount of polymer obtained was 4.00 g.

Example 9

Poly(2-(Methacryloyloxy)ethyl-tert-butylamine hydrochloride)

The procedure of example 1 was followed using the following reagents:2-(Methacryloxy)ethyl-tert-butylamine (30 g, 0.162 mole) in tert-butanol(68 mL), deionized water (22 mL),2,2′azobis(2-amidinopropane)dihydrochloride (0.220 g, 0.00081 mole). Thesolvent used for precipitation and washing of the polymer was hexane.The amount of polymer obtained was 21.9 g.

Example 10

Poly((3-acrylamidopropyl)trimethylammonium chloride-co-styrene) Mol %monomer composition: 60/40

The procedure of example 1 was followed using the following reagents:styrene (5.03 g, 0.048 mole) in ethanol (80 mL),3-acrylamidopropyltrimethylammonium chloride (19.96 g of a 75 percentsolution in water, 0.072 mole), 2,2′-azobisisobutyronitrile (0.198 g,0.0012 mole). The solvent used for precipitation and washing of thepolymer was acetone. The amount of polymer obtained was 14.5 g.

Example 11

Poly((3-methacrylamidopropyl)trimethylammoniumchloride-co-poly(dimethylsiloxane)monomethacrylate) Wt % monomercomposition: 90/10

The procedure of example 1 was followed using the following reagents:poly(dimethylsiloxane)monomethacrylate (Mn=9,000-12,000) (0.60 g) inisopropanol (18.6 mL), 3-methacrylamidopropyltrimethylammonium chloride(10.8 g of a 50 percent solution in water, 0.072 mole),2,2′-azobisisobutyronitrile (0.030 g, 0.00018 mole). The solvent usedfor precipitation and washing of the polymer was isopropanol. The amountof polymer obtained was 4.13 g.

Example 12

Poly((3-acrylamidopropyl)trimethylammoniumchloride-co-acrylamide-co-N-octadecylacrylamide) Mol % monomercomposition: 60/35/5

The procedure of example 1 was followed substituting the followingmaterials and amounts: octadecylacrylamide (79.38 g, 0.2453 mole) inisopropanol (3081.2 g), 3-acrylamidopropyltrimethylammonium chloride(811.41 g of a 75 percent solution in water, 2.944 mole), deionizedwater (406 mL), and acrylamide (122.06 g, 1.717 mole),2,2′-azobisisobutyronitrile (4.029 g, 0.0245 mole) in tetrahydrofuran(46 g). The amount of polymer obtained was 815 g.

Example 13

Poly((3-acrylamidopropyl)trimethylammoniumchloride-co-acrylamide-co-N-phenylacrylamide) Mol % monomer composition:25/70/5

The procedure of example 1 was followed substituting the followingmaterials and amounts: phenylacrylamide (33.82 g, 0.230 mole) intert-butanol (1000 g), 3-acrylamidopropyltrimethylammonium chloride(316.7 g of a 75 percent solution in water, 1.149 mole), deionized water(921 mL), acrylamide (228.67 g, 3.217 mole),2,2′azobis(2-amidinopropane)dihydrochloride (3.323 g, 0.0230 mole) indeionized water (24 g). The amount of polymer obtained was 532 g.

Example 14

Poly((3-acrylamidopropyl)trimethylammoniumchloride-co-acrylamide-co-N-methyl-N-octadecylacrylamide) Mol % monomercomposition: 25/70/5

The procedure of example 1 was followed using the following reagents:N-methyl-N-octadecylacrylamide (134.96 g, 0.400 mole) in tert-butanol(1892 g), 3-acrylamidopropyltrimethylammonium chloride (550.9 g of a 75percent solution in water, 2.00 mole), deionized water (1754 mL), andacrylamide (397.83 g, 5.597 mole),2,2′azobis(2-amidinopropane)dihydrochloride (6.163 g, 0.040 mole) indeionized water (32 g). The amount of polymer obtained was 1046 g.

Example 15

Poly(3-methyl-1-vinylimidazoliumchloride-co-acrylamide-co-dodecylacrylamide) Monomer Mole Ratio: 35/70/5

In a 500-mL flask equipped with an overhead mechanical stirrer and athermocouple probe, 1-vinylimidazole (270 g, 2.869 mole) was dissolvedin 2.7 L of anhydrous ethyl acetate. The solution was cooled to −10° C.,and methyl iodide was added (1425 g, 10.04 mole). Throughout thereaction the temperature was maintained at −10° C. using an ice saltbath. After the addition was complete, the reaction mixture was stirredfor 1 hour at −10° C., then brought to room temperature and allowed tostir for 16 hours. During this time off-white crystals formed in thesolution. The mixture was filtered and the crystalline solid was washedwith 10 L of anhydrous diethyl ether. This off-white solid was thenrecrystallized from n-propanol (melting point 68° C.). The crystallinesolid was then dissolved in 2.4 L of methanol to which was added 3.7 kgof Amberlite IRA-400 chloride ion exchange resin. The slurry was stirredfor 4 hours and then filtered. The filtrate was then concentrated undervacuum and then placed on a high vacuum pump to remove any remainingsolvent. The amount of 3-methyl-1-vinylimidazole chloride obtained was347.76 g. The procedure of example 1 was followed using the followingreagents: dodecylacrylamide (104.1 g, 0.435 mole) in tert-butanol (856g), 3-methyl-1-vinylimidazolium chloride (619 g of a 71.1 percentsolution in water, 3.0434 mole), deionized water (888.1 mL), acrylamide(370.9 g, 5.217 mole), 2,2′azobis(2-amidinopropane)dihydrochloride (11.8g, 0.04348 mole). The amount of polymer obtained was 813 g.

Example 16

Poly((3-acrylamidopropyl)trimethylammonium chloride-co-acrylamide) Mol %monomer composition: 50/50

A 5000-mL round-bottomed flask was fitted with an overhead stirrer, areflux condenser, and a thermocouple probe. The following materials wereplaced into the flask in the order specified:3-acrylamidopropyltrimethylammonium chloride (396.86 g of a 75 percentsolution in water, 1.44 mole), deionized water (1500 mL), and acrylamide(102.35 g, 1.44 mole). The resulting mixture was stirred atapproximately 23° C. A clear, slightly yellow solution resulted. Thesolution was sparged for at least 60 minutes with a vigorous nitrogenflow from an 18-gauge syringe needle whose tip was placed below thesurface of the stirring solution. Potassium metabisulfite (0.213 g,0.00096 mole) and potassium persulfate (0.259, 0.00096 mole) were theneach separately dissolved in a small amount of water and addedindividually to the solution. After 2-10 minutes, the temperature wasincreased to 60° C. The solution was stirred at 60° C. for 5-6 hours.The flask was then fitted with a distillation head and the solution washeated to 95° C. The vigorous nitrogen flow was resumed and 500 mL ofwater was distilled out of the flask in order to facilitate the work-upprocedure. The polymer solution was cooled and poured into 22 L ofisopropanol, resulting in precipitation of the polymeric product as acolorless solid. This mixture was stirred overnight, and the isopropanolwas decanted away from the polymer product. A fresh portion ofisopropanol was then added, and the mixture was stirred for 48 hours andthe isopropanol was decanted away from the polymer product. The polymerwas placed on a glass tray, and dried in a forced-air oven at 70° C. for24-48 hours. The dried solid was then ground to a fine powder using acommercial coffee grinder. The fine powder was placed into a glass trayin a forced air oven at 70° C. for 24-48 hours. A colorless solid (390.5g) was obtained.

Example 17

Poly((3-acrylamidopropyl)trimethylammonium chloride)

The procedure of example 16 was followed using the following reagents:3-acrylamidopropyltrimethylammonium chloride (533.3 g of a 75 percentsolution in water, 1.94 mole), deionized water (1467 mL), potassiummetabisulfite (0.143 g, 0.00065 mole) and potassium persulfate (0.174,0.00065 mole). The amount of polymer obtained was 372 g.

Example 18

Poly((3-acrylamidopropyl)trimethylammoniumchloride-co-N-vinyl-2-pyrrolidinone) Mol % monomer composition: 80/20

A 1000-mL round-bottomed flask was fitted with an overhead stirrer, areflux condenser, and a thermocouple probe. The following materials wereplaced into the flask in the order specified:3-acrylamidopropyltrimethylammonium chloride (141.04 g of a 75 percentsolution in water, 0.512 mole), deionized water (511 mL), andN-vinyl-2-pyrrolidinone (14.22 g, 0.128 mole). The resulting mixture wasstirred at approximately 23° C. A clear, slightly yellow solutionresulted. The solution was sparged for at least 60 minutes with avigorous nitrogen flow from an 18-gauge syringe needle whose tip wasplaced below the surface of the stirring solution. The radical initiator2,2′azobis(2-amidinopropane)dihydrochloride (1.20 g, 0.0044 mole) wasthen added to the solution and the temperature was increased to 60° C.The solution was stirred at 60° C. overnight. The solution was cooled toroom temperature and diluted with 600 mL of deionized water. Thesolution was then poured into a series of cellulose dialysis bags(Spectra/Por, molecular weight cutoff=6000-8000), and exhaustivelydialysed against deionized water. The polymer solution was removed fromthe dialysis bags, placed in a glass tray, and dried in a forced-airoven at 70° C. for 24-48 hours. The dried solid was then ground to afine powder using a commercial coffee grinder. The fine powder wasplaced into a glass tray in a forced air oven at 70° C. for 24-48 hours.A colorless solid (78 g) was obtained.

Example 19

Poly((3-acrylamidopropyl)trimethylammoniumchloride-co-N-ethylacrylamide) Mol % monomer composition: 50/50

A 250-mL round-bottomed flask was fitted with an overhead stirrer, areflux condenser, and a thermocouple probe. The following materials wereplaced into the flask in the order specified:3-acrylamidopropyltrimethylammonium chloride (19.36 g of a 75 percentsolution in water, 0.065 mole), deionized water (80 mL), andN-ethylacrylamide (6.48 g, 0.0654 mole). The resulting mixture wasstirred at approximately 23° C. A clear, slightly yellow solutionresulted. The solution was sparged for at least 30 minutes with avigorous nitrogen flow from an 18-gauge syringe needle whose tip wasplaced below the surface of the stirring solution. The radical initiator2,2′azobis(2-amidinopropane)dihydrochloride (0.177 g, 0.00065 mole) wasthen added to the solution and the temperature was increased to 60° C.The solution was stirred at 60° C. until it became a thick gel. Thesolution was then cooled to room temperature and poured into 3 L ofisopropanol, resulting in precipitation of the polymeric product as acolorless solid. This mixture was stirred overnight, and the isopropanolwas decanted away from the polymer product. A fresh 3-L portion ofisopropanol was then added, and the mixture was stirred for 6-8 hours.Again, the isopropanol was decanted away. The polymer was placed on aglass tray, and dried in a forced-air oven at 70° C. for 24-48 hours.The dried solid was then ground to a fine powder using a commercialcoffee grinder. The fine powder was placed into a glass tray in a forcedair oven at 70° C. for at least 24 hours. A colorless solid (15.5 g) wasobtained.

Example 20

Poly(diallyldimethylammonium chloride-co-acrylic acid) Monomer MoleRatio: 90/10

The procedure of example 19 was followed using the following reagents:diallyldimethylammonium chloride (1465.9 g of a 65 percent solution inwater, 5.89 mole), deionized water (3486.9 mL), acrylic acid (47.19 g,0.655 mole), 2,2′azobis(2-amidinopropane)dihydrochloride (8.88 g, 0.0327mole). The amount of polymer obtained was 632 g.

Example 21

Poly((3-acrylamidopropyl)trimethylammoniumchloride-co-O-acryloyl-O′-methylpolyethylene glycol 5,000) Wt % monomercomposition: 89/11

A procedure similar to example 19 was followed using the followingreagents: 3-acrylamidopropyltrimethylammonium chloride (1187 g of a 75percent solution in water, 4.31 mole), deionized water (3703 mL), andO-acryloyl-O′-methylpolyethylene glycol 5,000 (109.7 g, 0.022 mole),2,2′azobis(2-amidinopropane)dihydrochloride (5.869 g, 0.0216 mole) indeionized water (30 g). The amount of polymer obtained was 928 g.

Example 22

Poly(3-methyl-1-vinylimidazolium chloride-co-acrylamide) Monomer MoleRatio: 50/50

The procedure of example 19 was followed using the following reagents:3-methyl-1-vinylimidazolium chloride (268.18 g, 1.855 mole), deionizedwater (933 mL), acrylamide (131.8 g, 1.855 mole),2,2′azobis(2-amidinopropane)dihydrochloride (5.030 g, 0.0186 mole). Theamount of polymer obtained was 382 g.

Example 23

Poly(N,N-diallyl-2-hydroxyethylamine)

A 50-mL round-bottomed flask was fitted with a magnetic stirrer, areflux condenser, and a thermocouple probe. The following materials wereplaced into the flask in the order specified:N,N-diallyl-2-hydroxyethylamine (10 g), concentrated HCl (7 g),deionized water (3 mL). The solution was degassed for 30 minutes bybubbling with nitrogen from an 18-gauge needle.2,2′Azobis(2-amidinopropane)dihydrochloride (0.095 g, 0.00035 mole) wasthen added and the solution was heated to 60° C. The solution wasstirred at 60° C. overnight. The solution was then cooled to roomtemperature and poured into 1 L of isopropanol, resulting inprecipitation of the polymeric product as a colorless solid. Thismixture was stirred for 1-3 hours, and the isopropanol was decanted awayfrom the polymer product. A fresh 1-L portion of isopropanol was thenadded, and the mixture was stirred for 3-6 hours. Again, the isopropanolwas decanted away, and another 1-L portion of fresh isopropanol wasadded to the polymer. The mixture was stirred overnight and theisopropanol was decanted away from the polymer product. The polymer wasplaced on a glass tray, and dried in a forced-air oven at 70° C. for24-48 hours. The dried solid was then ground to a fine powder using acommercial coffee grinder. The fine powder was placed into a glass trayin a forced air oven at 70° C. for at least 24 hours. A colorless solid(8 g) was obtained.

No Examples 24 and 25 Example 26

Modification of poly(2-ethyl-2-oxazoline) by Partial Hydrolysis

A 250-mL flask was equipped with an overhead mechanical stirrer,condenser and a thermocouple probe. The following materials were placedinto the flask in the order specified: poly(2-ethyl-2-oxazoline) (25 g),deionized water (95 mL), concentrated HCl (9.8 g). The solution washeated to reflux with stirring for 8 hours. The solution was then pouredinto 1.5 L of acetone resulting in the precipitation of the polymericproduct. The mixture was stirred for 1 hour. The acetone was thendecanted away and a fresh 1.5-L portion of acetone was added. After 2hours of stirring, the acetone was decanted away, and the solid wasblended in a commercial blender containing fresh acetone. The solid wascollected by filtration and suspended in fresh acetone overnight. Thesolid was then collected and placed on a glass tray, and dried in aforced-air oven at 70° C. for 24-48 hours. The dried solid was thenground to a fine powder using a commercial coffee grinder. The finepowder was placed into a glass tray in a forced air oven at 70° C. forat least 24 hours. A colorless solid (30.04 g) was obtained.

Example 27

Modification of poly(allylamine) HCl with 100 mol % Glycidol

Poly(allylamine) HCl (60g of 50 percent aqueous solution, 0.321 molemonomer equivalents) was dissolved in 80 mL of water and was then heatedto 50° C. in a 500-mL flask equipped with an overhead mechanicalstirrer, condenser and a thermocouple probe. The pH of the solution wasadjusted to 10 by the addition of NaOH (50 percent solution). Glycidol(23.77 g 0.321 mol) was added slowly to the stirred solution. A largeexotherm was observed during the addition of the glycidol. This mixturewas then heated at 50° C. for 3 hours giving a very viscous solution.The reaction mixture was cooled and then poured into a dialysis bag(Spectra/Por; molecular weight cut off 6000-8000) and dialyzed against19 liters of deionized water. The dialysis solution was changed until aconductivity of <1 mS/cm was recorded. The contents of the dialysis bagwere then placed in a beaker and the pH of the solution adjusted to avalue <2 with concentrated HCl. This solution was then transferred todrying trays and placed in a convection oven at 70° C. for 24 hours. Thedried solid was ground to a fine powder using a lab mill and then passedthrough a sieve (80 mesh). The product was then replaced in a convectionoven at 70° C. for 48 hours to remove any residual solvent. Yield=47.2g.

Example 28

Modification of poly(allylamine) HCl with 200 mol % Glycidol

The procedure of example 27 was followed using the following materials:Poly(allylamine) HCl (60 g of 50 percent aqueous solution, 0.321 molemonomer equivalents), deionized water (80 mL), glycidol (47.54 g, 0.642mole). The amount of polymer obtained was 66.8 g.

Example 29

Modification of poly(allylamine) HCl with 300 mol % Glycidol

The procedure of example 27 was followed using the following materials:Poly(allylamine) HCl (40 g of 50 percent aqueous solution, 0.214 molemonomer equivalents), deionized water (80 mL), glycidol (47.54 g, 0.642mole). The amount of polymer obtained was 48.9 g.

Example 30

Modification of poly(diallylamine) HCl with Glycidol

The procedure of example 27 was followed using the following materials:Poly(diallylamine) HCl (106.8 g of 28.1 percent aqueous solution, 0.225mole monomer equivalents), deionized water (43.2 mL), glycidol (41.57 g,0.561 mole). The amount of polymer obtained was 56.3 g.

Example 31

40 Mol % Modification of poly(diallylmethylamine) HCl with2-chloroaceticic acid

In a 500-mL flask equipped with an overhead mechanical stirrer,condenser and a thermocouple probe, poly(diallylmethylamine), (120 g ofa 44.22 percent aqueous solution 0.359 mole monomer equivalents) wasdissolved in 60 mL of deionized water and 225 mL ethanol. The solutionwas heated to 70° C. The pH of the solution was adjusted to 10 by theaddition of NaOH (50 percent solution). 2-Chloroacetic acid (13.58 g,0.144 mole) was then added in one portion. The reaction mixture wasstirred at 70° C. for 16-18 hours. The pH of the solution was checkedperiodically during this time and was maintained at 10 by the additionof 50 percent NaOH. The solution was then cooled to room temperature,transferred to a dialysis bag (Spectra/Por molecular weight cut off6000-8000) and dialyzed against 19 liters of deionized water. Thedialysis solution was changed until a conductivity of <1 mS/cm wasrecorded. The contents of the dialysis bag was then placed in a beakerand the pH of the solution adjusted to a value <2 with concentrated HCl.This solution was then transferred to drying trays and placed in aconvection oven at 70° C. for 24 hours. The dried solid was ground to afine powder using a lab mill and then passed through a sieve (80 mesh).The product was then replaced in a convection oven at 70° C. for 48hours to remove any residual solvent. The amount of polymer obtained was55.5 g.

Example 32

30 Mol % Modification of poly(diallylmethylamine) HCl with2-chloroaceticic acid

The procedure of example 31 was followed using the following materials:poly(diallylmethylamine) HCl (120 g of 44.22 percent aqueous solution,0.359 mole monomer equivalents), deionized water (60 mL), ethanol (225mL), 2-chloroacetic acid (10.19 g, 0.108 mole). The amount of polymerobtained was 53.8 g.

Example 33

20 Mol % Modification of poly(diallylmethylamine) HCl with2-chloroaceticic acid

The procedure of example 31 was followed using the following materials:poly(diallylmethylamine) HCl (62.9 g of 44.22 percent aqueous solution,0.188 mole monomer equivalents), deionized water (30 mL), ethanol (110mL), 2-chloroacetic acid (3.56 g, 0.038 mole). The amount of polymerobtained was 13.53 g.

Example 34

Modification of poly(diallylmethylamine) HCl with 3-bromopropionic acid

In a 500-mL flask equipped with an overhead mechanical stirrer,condenser and a thermocouple probe, poly(diallylmethylamine), (67.84 gof a 44.22 percent aqueous solution 0.203 mole monomer equivalents) wasdissolved in 60 mL of deionized water and 120 mL ethanol. The solutionwas heated to 70° C. The pH of the solution was adjusted to 10 by theaddition of NaOH (50 percent solution). 3-Bromopropionic acid (32.63 g,0.213 mole) was then added in one portion. The reaction mixture wasstirred at 70° C. for 16-18 hours. The pH of the solution was checkedperiodically during this time and was maintained at 10 by the additionof 50 percent NaOH. The solution was then cooled to room temperature,transferred to a dialysis bag (Spectra/Por molecular weight cut off6000-8000) and dialyzed against 19 liters of deionized water. Thedialysis solution was changed until a conductivity of <1 mS/cm wasrecorded. The contents of the dialysis bag was then placed in a beakerand the pH of the solution adjusted to a value <2 with concentrated HCl.This solution was then transferred to drying trays and placed in aconvection oven at 70° C. for 24 hours. The dried solid was ground to afine powder using a lab mill and then passed through a sieve (80 mesh).The product was then replaced in a convection oven at 70° C. for 48hours to remove any residual solvent. The amount of polymer obtained was35 g.

Example 35

Modification of poly(diallylmethylamine) HCl with 4-bromobutyric acid

The procedure of example 34 was followed using the following materials:poly(diallylmethylamine) HCl (67.84 g of 44.22 percent aqueous solution,0.203 mole monomer equivalents), deionized water (60 mL), ethanol (130mL), 4-bromobutyric acid (35.63 g, 0.213 mole). The amount of polymerobtained was 73 g.

Example 36

Modification of poly(allylamine) HCl with 3-bromopropionic acid

The procedure of example 34 was followed using the following materials:poly(allylamine) HCl (40 g of a 50 percent aqueous solution, 0.214 molemonomer equivalents), deionized water (50 mL), 3-bromopropionic acid(34.36 g, 0.225 mole). The amount of polymer obtained was 28.5 g.

Example 37

Modification of poly(allylamine) HCl with 4-bromobutyric acid

The procedure of example 34 was followed using the following materials:poly(allylamine) HCl (40 g of a 50 percent aqueous solution, 0.214 molemonomer equivalents), deionized water (50 mL), 4-bromobutyric acid (39.4g, 0.236 mole). The amount of polymer obtained was 20.6 g.

Example 38

Modification of polyethylenimine with 3-bromopropionic acid

The procedure of example 34 was followed using the following materials:polyethylenimine (30 g of a 50 percent aqueous solution, 0.348 molemonomer equivalents), deionized water (45 mL), 3-bromopropionic acid(55.9 g, 0.365 mole). The amount of polymer obtained was 37.3 g.

Example 39

Polydiallylamine hydrochloride

Diallylamine (2000.3 g) was added slowly over a period of 2 days toconcentrated HCl (2035.6 g). The temperature of the reaction wasmaintained below 10° C. by cooling the flask in an ice-salt-water bath,and by adjusting the addition rate. The room temperature pH of theresulting diallylamine hydrochloride solution (68.16 percentdiallylamine hydrochloride) was 0.005.

To a 12-L 4-necked round-bottomed flask equipped with an overheadstirrer and an air condenser, was added diallylamine hydrochloride(3667.8 g of a 68.16 percent solution), and deionized water (4665.5 g).The resulting solution had pH 0.74. To the flask was added NaOH (66.8 gof a 50 percent aqueous solution). The resulting solution had pH 2.55.Nitrogen gas was bubbled through the solution, via a stainless steelneedle, with stirring, and venting on top of the air condenser for 2hours. The nitrogen line was put on top of the air condenser withpositive pressure from a mineral oil bubbler. To the flask was added125.0 g of freshly made 20 percent2,2′-azobis(2-amidinopropane)dihydrochloride in deionized water. Thiswas added via syringe through a septum. The2,2′-azobis(2-amidinopropane)dihydrochloride solution was not degassedwith nitrogen. The solution was heated to 60° C. over a period of 1 hour8 minutes., with a heating mantle connected to a J-Kem temperaturecontroller. The solution was heated at 60° C. for 18 hours. The reactiontemperature rose to 64° C., and slowly cooled back down to 60° C. over a3 hours period. After the first 18-hour heating period, the reactionsolution was allowed to cool down slowly to 49° C., and to the flask wasadded 125.0 g of freshly made 20 percent2,2′-azobis(2-amidinopropane)dihydrochloride in deionized water. Thesolution was heated to 60° C. over a period of about 15 minutes, with aheating mantle connected to a J-Kem temperature controller. The solutionwas heated at 60° C. for 18 hours. The reaction temperature rose to 62°C., and slowly cooled back down to 60° C. over a 1 hour period. Afterthe second 18 hours heating period, the reaction solution was allowed tocool down slowly to 40° C., and to the flask was added 125.0 g offreshly made 20 percent 2,2′-azobis(2-amidinopropane)dihydrochloride indeionized water. The solution was heated to 60° C. over a period ofabout 15 minutes, with a heating mantle connected to a J-Kem temperaturecontroller. The solution was heated at 60° C. for 18 hours. The reactiontemperature rose to 63° C., and slowly cooled back down to 60° C. over a1 hour period. After cooling to room temperature, the solution was adark orange viscous, flowable, clear solution. The flask contents werecombined with deionized water (4166.7 g). The resulting solution had pH4.41. SEC analysis: Mw 61,500 Daltons; polydispersity 2.43.

Example 40

Polydiallylmethylamine

Diallylmethylamine (361.0 g) was added slowly over a period of 2 hours,10 minutes to concentrated HCl (320.3 g). The temperature of thereaction was maintained below 10° C. by cooling the flask in anice-salt-water bath, and by adjusting the addition rate. The roomtemperature pH of the resulting diallylmethylamine hydrochloridesolution was 6.492, and the solution had two phases, a small oil phase(top) with a large aqueous phase (bottom). To 660.5 g of this mixturewas added concentrated HCl (22.6 g), and the pH of the final solutionwas 0.349. The final solution was a single phase, and contains 68.04percent diallylmethylamine hydrochloride by weight.

To a 500-mL three-necked round-bottomed flask equipped with an overheadstirrer and a vigreux column, was added diallylmethylamine hydrochloride(73.5 g of a 68.04 percent solution), and deionized water (26.5 g). Theresulting solution had pH 0.871. To the flask was added 50 percentaqueous NaOH until the resulting solution had pH 2.53. Nitrogen gas wasbubbled through the solution, via a stainless steel needle, withstirring, and venting on top of the vigreux column for 30 minutes Thenitrogen line was put on top of the vigreux column with positivepressure from a mineral oil bubbler. To the flask was added 2.5 g offreshly made 20 percent 2,2′-azobis(2-amidinopropane)dihydrochloride indeionized water. This was added via a transfer pipette, through one ofthe flask necks with a strong nitrogen flow. The2,2′-azobis(2-amidinopropane)dihydrochloride solution was not degassedwith nitrogen. The reaction solution was heated to 60° C. over a periodof 30 minutes, with a heating mantle connected to a J-Kem temperaturecontroller. The reaction solution was heated at 60° C. for 18 hours.After the first 18-hour heating period, the reaction solution wasallowed to cool down slowly to room temperature, and to the flask wasadded 2.5 g of freshly made 20 percent2,2′-azobis(2-amidinopropane)dihydrochloride in deionized water. Thereaction solution was heated to 60° C. over a period of about 30minutes. The reaction solution was heated at 60° C. for another 18hours. After the second 18-hourheating period, the reaction solution wasallowed to cool down slowly to room temperature, and to the flask wasadded 2.5 g of freshly made 20 percent2,2′-azobis(2-amidinopropane)dihydrochloride in deionized water. Thereaction solution was heated to 60° C. over a period of about 30minutes. The reaction solution was heated at 60° C. for another 18hours. After cooling to room temperature, the reaction solution was aclear dark orange, viscous and flowable solution. The flask contentswere combined with deionized water (150.0 g). The resulting solution hadpH 4.36. SEC analysis: Mw 54,100 Daltons; polydispersity 2.13.

Example 41

Functionalization of poly(ethylene-alt-maleic anhydride) with3-(dimethylamino)propylamine

To a solution of poly(ethylene-alt-maleic anhydride) (20.0 g) inN,N-dimethylformamide (180 mL) under a nitrogen atmosphere was added3-(dimethylamino)propylamine (40 mL). The mixture was heated at 60° C.overnight and allowed to cool to room temperature. Concentrated HCl (47g) was added and the mixture was transferred to a Spectra/Por 1 dialysismembrane bag (molecular weight cutoff 6000 to 8000) and dialyzed againstdeionized water for at least 18 hours. The dialyzed polymer solution wasdried in a forced-air oven at 70° C. for 48 hours to afford 37.8 g.

No Example 42 Example 43

Functionalization of poly(diallylmethylamine) withpolyoxyethylene(40)nonylphenyl glycidyl ether

Polyoxyethylene(40)nonylphenyl glycidyl ether was synthesized byreacting polyoxyethylene(40)nonylphenyl ether (100.0 g) withepichlorohydrin (60 mL) in the presence of deionized water (0.750 g),NaOH (6 g), and 3,5-di-tert-butyl-4-hydroxyanisole (0.23 g) at 60° C.for 10 hours. After cooling to room temperature, methylene chloride (200mL) was added, and this solution was extracted with a solution ofdeionized water (200 mL) and potassium dihydrogen phosphate (10 g). Theorganic layer was washed four times with deionized water (100 mL perwash) and concentrated on a rotary evaporator (60° C. bath temperature).The residue was triturated with diethyl ether (1 L) and dried undervacuum at 50° C. to afford 83.0 g.

A basic solution of polydiallylmethylamine was prepared by mixingpolydiallylmethylamine hydrochloride (677 g of a 44.22 percent aqueoussolution), deionized water (823 g) and NaOH (87 g of a 50 percentaqueous solution) overnight.

To a portion of the polydiallylmethylamine basic solution (158.9.0 g)was added polyoxyethylene(40)nonylphenyl glycidyl ether (3.0 g). Afterstirring overnight, concentrated HCl (25.0 g) was added. The reactionmixture was transferred to a Spectra/Por 1 dialysis membrane bag(molecular weight cutoff 6000 to 8000) and dialyzed against deionizedwater for at least 18 hours. The dialyzed polymer solution was dried ina forced-air oven at 70° C. for 48 hours to afford 31.5 g.

Example 44

Functionalization of poly(diallylmethylamine) withpolyoxyethylene(40)nonylphenyl glycidyl ether

To a portion of the polydiallylmethylamine basic solution (158.7 g;Example 43) was added polyoxyethylene(40)nonylphenyl glycidyl ether (6.0g; Example 43). After stirring overnight, concentrated HCl (18.0 g) wasadded. The reaction mixture was transferred to a Spectra/Por 1 dialysismembrane bag (molecular weight cutoff 6000 to 8000) and dialyzed againstdeionized water for at least 18 hours. The dialyzed polymer solution wasdried in a forced-air oven at 70° C. to afford 33.4 g.

Example 45

Functionalization of poly(diallylmethylamine) withpolyoxyethylene(40)nonylphenyl glycidyl ether

To a portion of the polydiallylmethylamine basic solution (158.7 g;Example 43) was added polyoxyethylene(40)nonylphenyl glycidyl ether (9.0g; Example 43). After stirring overnight, concentrated HCl (32.6 g) wasadded. The reaction mixture was transferred to a Spectra/Por 1 dialysismembrane bag (molecular weight cutoff 6000 to 8000) and dialyzed againstdeionized water for at least 18 hours. The dialyzed polymer solution wasdried in a forced-air oven at 70° C. to afford 37.3 g.

Example 46

Functionalization of poly(diallylmethylamine) withpolyoxyethylene(40)nonylphenyl glycidyl ether

To a portion of the polydiallylmethylamine basic solution (158.7 g;Example 43) was added polyoxyethylene(40)nonylphenyl glycidyl ether(12.0 g; Example 43). After stirring overnight, concentrated HCl (24.2g) was added. The reaction mixture was transferred to a Spectra/Por 1dialysis membrane bag (molecular weight cutoff 6000 to 8000) anddialyzed against deionized water for at least 18 hours. The dialyzedpolymer solution was dried in a forced-air oven at 70° C. to afford 40.6g.

Example 47

Functionalization of poly(diallylmethylamine) withpolyoxyethylene(40)nonylphenyl glycidyl ether

To a portion of the polydiallylmethylamine basic solution (158.7 g;Example 43) was added polyoxyethylene(40)nonylphenyl glycidyl ether (30g; Example 43). After stirring overnight, concentrated HCl was addeduntil the pH of the resulting solution was less than 1.0. The reactionmixture was transferred to a Spectra/Por 1 dialysis membrane bag(molecular weight cutoff 6000 to 8000) and dialyzed against deionizedwater for at least 18 hours. The dialyzed polymer solution was dried ina forced-air oven at 70° C. to afford 60.0 g.

No Example 48 Example 49

Functionalization of poly(diallylmethylamine) withpolyoxyethylene(23)lauryl glycidyl ether

Polyoxyethylene(23)lauryl glycidyl ether was synthesized by reactingpolyoxyethylene (23)lauryl ether (50.0 g) with epichlorohydrin (50 mL)in the presence of deionized water (0.625 g), NaOH (5 g), and3,5-di-tert-butyl-4-hydroxyanisole (0.28 g) at 60° C. for 10 hours.After cooling to room temperature, methylene chloride (100 mL) wasadded, and this solution was extracted with a solution of deionizedwater (100 mL) and potassium dihydrogen phosphate (5 g). The organiclayer was washed four times with deionized water (100 mL per wash) andconcentrated on a rotary evaporator (60° C. bath temperature). Theresidue was triturated with diethyl ether (1 L) and dried under vacuumto afford 34.55 g.

A basic solution of polydiallylmethylamine was prepared by mixingpolydiallylmethylamine hydrochloride (677 g of a 44.22 percent aqueoussolution), deionized water (823 g) and NaOH (87 g of a 50 percentaqueous solution) overnight.

To a portion of the polydiallylmethylamine basic solution (158.7 g) wasadded polyoxyethylene(23)lauryl glycidyl ether (3.0 g). After stirringovernight, concentrated HCl (40.3 g) was added. The reaction mixture wastransferred to a Spectra/Por 1 dialysis membrane bag (molecular weightcutoff 6000 to 8000) and dialyzed against deionized water for at least18 hours. The dialyzed polymer solution was dried in a forced-air ovenat 70° C. to afford 31 g.

Example 50

Functionalization of poly(diallylmethylamine) withpolyoxyethylene(23)lauryl glycidyl ether

To a portion of the basic solution of polydiallylmethylamine (158.7 g;Example 49) was added polyoxyethylene(23)lauryl glycidyl ether (6.0 g;Example 49). After stirring for 24 hours at room temperature,concentrated HCl (21.6 g) was added. The reaction mixture wastransferred to a Spectra/Por 1 dialysis membrane bag (molecular weightcutoff 6000 to 8000) and dialyzed against deionized water for at least18 hours. The dialyzed polymer solution was dried in a forced-air ovenat 70° C. to afford 30.0 g.

Example 51

Functionalization of poly(diallylmethylamine) with glycidol

A basic solution of polydiallylmethylamine was prepared by mixingpolydiallylmethylamine hydrochloride (615.4 g of a 44.22 percent aqueoussolution), deionized water (745.2 g) and NaOH (78.0 g of a 50 percentaqueous solution) overnight.

To a portion of the basic solution of polydiallylmethylamine (158.7 g)was added glycidol (26.9 mL). After stirring for 24 hours at roomtemperature, concentrated HCl (14.2 g) was added. The reaction mixturewas transferred to a Spectra/Por 1 dialysis membrane bag (molecularweight cutoff 6000 to 8000) and dialyzed against deionized water for atleast 18 hours. The dialyzed polymer solution was dried in a forced-airoven at 70° C. to afford 40.0 g.

Example 52

Functionalization of poly(diallylmethylamine) with glycidol

To a portion of the basic solution of polydiallylmethylamine (158.7 g;Example 51) was added glycidol (13.5 mL). After stirring for 24 hours atroom temperature, concentrated HCl (13.5 g) was added. The reactionmixture was transferred to a Spectra/Por 1 dialysis membrane bag(molecular weight cutoff 6000 to 8000) and dialyzed against deionizedwater for at least 18 hours. The dialyzed polymer solution was dried ina forced-air oven at 70° C. to afford 40.0 g.

Example 53

Functionalization of poly(diallylmethylamine)

To a portion of the basic solution of polydiallylmethylamine (158.7 g;Example 51) was added bromoethane (30.30 mL). After stirring for 24hours at room temperature, concentrated HCl (10.9 g) was added. Thereaction mixture was transferred to a Spectra/Por 1 dialysis membranebag (molecular weight cutoff 6000 to 8000) and dialyzed againstdeionized water for at least 18 hours. The dialyzed polymer solution wasdried in a forced-air oven at 70° C. to afford 31.0 g.

Example 54

Polyethylenimine, 80% ethoxylated

A solution of polyethylenimine, 80 percent ethoxylated (269.1 g of a35-40 percent solution in water; Aldrich Chemical Company) wastransferred to a Spectra/Por 1 dialysis membrane bag (molecular weightcutoff 6000 to 8000) and dialyzed against deionized water for at least18 hours. The dialyzed polymer solution was dried in a forced-air ovenat 70° C. to afford the desired compound.

Example 55

Copoly(N-[3-(dimethylamino)propyl]acrylamide/acrylamide/N-dodecylacrylamide)(48:48:5)

A solution of N-[3-(dimethylamino)propyl]acrylamide (30.0 g), acrylamide(13.6 g), and N-dodecylacrylamide (4.6 g) in deionized water (50 mL) andethanol (50 mL) was heated to 60° C. under a nitrogen atmosphere. Whenthe solution reached 60° C.,2,2′-azobis(2-amidinopropane)dihydrochloride (2.4 g of a 20 percentaqueous solution) was added. Heating was continued for 18 hours under anitrogen atmosphere. After cooling to room temperature, the reactionsolution was dissolved in isopropanol 150 mL), and concentrated HCl(29.5 g) was added with stirring. The solution was decanted from theprecipitated polymer. The polymer was suspended in isopropanol (500 mL),stirred for at least 15 minutes, and allowed to settle. After decanting,the polymer was similarly washed an additional 3 times with isopropanol.The washed polymer was dried in a forced-air oven at 70° C. to afford81.1 g.

Example 56

Copoly(N-[3-(dimethylamino)propyl]acrylamide/acrylamide) (50/50)

A solution of N-[3-(dimethylamino)propyl]acrylamide (30.0 g) andacrylamide (13.6 g) in deionized water (40 mL) and ethanol (40 mL) washeated to 60° C. under a nitrogen atmosphere. When the solution reached60° C., 2,2′-azobis(2-amidinopropane)dihydrochloride (2.2 g of a 20percent aqueous solution) was added. Heating was continued for 18 hoursunder a nitrogen atmosphere. After cooling to room temperature, thereaction solution was dissolved in isopropanol (150 mL), andconcentrated HCl (31.5 g) was added with stirring. The solution wasdecanted from the precipitated polymer. The polymer was suspended inisopropanol (500 mL), stirred for at least 15 minutes, and allowed tosettle. After decanting, the polymer was similarly washed an additional3 times with isopropanol. The washed polymer was dried in a forced-airoven at 70° C. to afford 68.2 g.

Example 57

Copoly(N-[3-(dimethylamino)propyl]acrylamide/acrylamide/N-dodecylacrylamide)(75/20/5)

A solution of N-[3-(dimethylamino)propyl]acrylamide (22.5 g), acrylamide(2.7 g), and N-dodecylacrylamide (2.3 g) in deionized water (30 mL) andethanol (30 mL) was heated to 60° C. under a nitrogen atmosphere. Whenthe solution reached 60° C.,2,2′-azobis(2-amidinopropane)dihydrochloride (1.4 g of a 20 percentaqueous solution) was added. Heating was continued for 18 hours under anitrogen atmosphere. After cooling to room temperature, the reactionsolution was dissolved in isopropanol (150 mL), and concentrated HCl(29.2 g) was added with stirring. The solution was decanted from theprecipitated polymer. The polymer was suspended in isopropanol (500 mL),stirred for at least 15 minutes, and allowed to settle. After decanting,the polymer was similarly washed an additional 3 times with isopropanol.The washed polymer was dried in a forced-air oven at 70° C. to afford34.7 g.

Example 58

Functionalization of polydiallylamine with(6-bromohexyl)trimethylammonium bromide

A solution of polydiallylamine hydrochloride (106.8 g of a 28.09 percentaqueous solution), deionized water (400 g), NaOH (9.6 g of a 50 percentaqueous solution), and (6-bromohexyl)trimethylammonium bromide (51.1 g)was heated to 60° C. for 18 hours. After 1 hour at 60° C., NaOH (4.5 gof a 50 percent aqueous solution) was added. After 1.5 hours at 60° C.,NaOH (4.5 g of a 50 percent aqueous solution) was added. After 2 hoursat 60° C., NaOH (4.5 g of a 50 percent aqueous solution) was added.Concentrated HCl was added until the reaction solution had a pH <1. Thesolution was then poured into isopropanol (4 L) and stirred for at least15 minutes. The solution was decanted from the precipitated polymer. Thepolymer was suspended in isopropanol (4 L), stirred for at least 15minutes, and allowed to settle. After decanting, the polymer wassimilarly washed an additional time with isopropanol. The washed polymerwas dried in a forced-air oven at 70° C. to afford 69.4 g.

Example 59

Functionalization of poly(diallylmethylamine) with poly(ethyleneglycol)diglycidyl ether

A basic solution of polydiallylmethylamine was prepared by mixingpolydiallylmethylamine hydrochloride (615.4 g of a 44.22 percent aqueoussolution), deionized water (745.2 g) and NaOH (78.0 g of a 50 percentaqueous solution) overnight. To a portion of the polydiallylmethylaminebasic solution (158.6 g ) was added poly(ethylene glycol)diglycidylether (9.0 g, Average Mn ca. 526, from Aldrich Chemical Co.). Afterstirring overnight, concentrated HCl (10 mL) was added. The reactionmixture was transferred to a Spectra/Por 1 dialysis membrane bag(molecular weight cutoff 6000 to 8000) and dialyzed against deionizedwater for at least 18 hours. The dialyzed polymer solution was dried ina forced-air oven at 70° C. to afford 9.3 g.

Example 60

Poly[bis(2-chloroethyl)ether-alt-1,3-bis[3-(dimethylamino)propyl]urea],Quaternized

A solution ofpoly[bis(2-chloroethyl)ether-alt-1,3-bis[3-(dimethylamino)propyl]urea],quaternized (566.7 g of a 62 percent solution in water; from AldrichChemical Co.) was transferred to a Spectra/Por 1 dialysis membrane bag(molecular weight cutoff 6000 to 8000) and dialyzed against deionizedwater for at least 18 hours. The dialyzed polymer solution was dried ina forced-air oven at 70° C. to afford the desired compound.

Example 61

Functionalization of polyethylenimine with glycidol

A solution of polyethylenimine (60.0 g), deionized water (240 g), andglycidol (46.2 mL) was heated at 50° C. under a nitrogen atmosphere for18 hours. After cooling to room temperature, concentrated HCl (50 mL)was added. The reaction was transferred to a Spectra/Por 1 dialysismembrane bag (molecular weight cutoff 6000 to 8000) and dialyzed againstdeionized water for at least 18 hours. The dialyzed polymer solution wasdried in a forced-air oven at 70° C. to afford the desired compound.

Example 62

Functionalization of polyethylenimine with 2-bromoethanol

A solution of polyethylenimine (60.0 g), deionized water (240 g), and2-bromoethanol (49.4 mL) was heated at 50° C. under a nitrogenatmosphere for 18 hours. After 1.5 hours at 50° C., NaOH (31.9 g of a 50percent aqueous solution) was added. After cooling to room temperature,concentrated HCl (30 mL) was added. The reaction mixture was transferredto a Spectra/Por 1 dialysis membrane bag (molecular weight cutoff 6000to 8000) and dialyzed against deionized water for at least 18 hours. Thedialyzed polymer solution was dried in a forced-air oven at 70° C. toafford the desired compound.

Example 63

Protonation of polydiallylmethylamine with L-tartaric acid

A basic solution of polydiallylmethylamine was prepared by mixingpolydiallylmethylamine hydrochloride (615.4 g of a 44.22 percent aqueoussolution), deionized water (745.2 g) and NaOH (78.0 g of a 50 percentaqueous solution) overnight.

To a portion of the polydiallylmethylamine basic solution (158.6 g) wasadded L-tartaric acid (30.8 g). After stirring overnight, the solutionwas poured into isopropanol (3 L) and stirred for at least 15 minutes.The solution was decanted from the precipitated polymer. The polymer wassuspended in isopropanol (3 L), stirred for at least 15 minutes, andallowed to settle. After decanting, the polymer was similarly washed anadditional time with isopropanol. The washed polymer was dried in aforced-air oven at 70° C. to afford 45.2 g.

Example 64

Polydiallyldimethylammonium chloride

Polydiallyldimethylammonium chloride (526.8 g of a 20 percent aqueoussolution, average MW 200,000-350,000, from Aldrich Chemical Co.) waspoured into isopropanol (12 L) and stirred for at least 15 minutes. Thesolution was decanted from the precipitated polymer. The washed polymerwas dried in a forced-air oven at 70° C. to afford 90.8 g.

Example 65

Functionalization of poly(diallylmethylamine) withpolyoxyethylene(2,000)methyl glycidyl ether

NaH (3.28 g; 60 percent in oil from VWR) was weighed out in athree-necked 1-L round-bottomed flask and washed 3 times with 200 mL ofhexane. The hexane was removed and the NaH was suspended in 350 mL ofanhydrous dioxane. Polyoxyethylene(2,000)methyl glycidyl ether (130 g;average Mn 2,000, obtained from Aldrich Chemical Co.) was dissolved in250 mL of dioxane and then added to the above stirred solution at roomtemperature under a nitrogen atmosphere. The solution was stirred for afurther hour at room temperature. The reaction mixture was heated to 45°C. and then 12.03 g of epichlorohydrin was added to this solution andthe reaction mixture was heated overnight. The reaction was allowed tocool to room temperature and was then filtered. The filtered solutionwas concentrated using a rotary evaporator to give a white solid. Thesolid was dissolved in 500 mL of methylene chloride and the polymer wasprecipitated in 4 L of diethyl ether. The polymer was dissolved in 500mL of methylene chloride and the polymer was precipitated in 4 L ofdiethyl ether and filtered. The polymer was dried in a vacuum oven atroom temperature over 72 hours to afford 110.9 g ofpolyoxyethylene(2,000)methyl glycidyl ether. A solution ofpolydiallylmethylamine hydrochloride (67.7 g of a 44.22 percent aqueoussolution), deionized water (82.3 g) and NaOH (8.7 g of a 50 percentaqueous solution) was heated at 60° C. for 3.5 hours.Polyoxyethylene(2,000)methyl glycidyl ether (1.5 g) was then added andthe solution was heated at 60° C. for an additional 8 hours. Aftercooling to room temperature, the reaction mixture was poured intoacetone (4 L) and stirred for at least 15 minutes. The solution wasdecanted from the precipitated polymer. The polymer was suspended inacetone (2 L), stirred for at least 15 minutes, and allowed to settle.After decanting, the polymer was similarly washed an additional timewith acetone. The washed polymer was dried in a forced-air oven at 70°C. to afford 26.4 g.

No Example 66 Example 67

Functionalization of poly(diallylmethylamine) withpolyoxyethylene(2,000)methyl glycidyl ether

A solution of polydiallylmethylamine hydrochloride (67.7 g of a 44.22percent aqueous solution), deionized water (82.3 g) and NaOH (8.7 g of a50 percent aqueous solution) was heated at 60° C. for 3.5 hours.Polyoxyethylene(2,000)methyl glycidyl ether (3.0 g) was then added andthe solution was heated at 60° C. for an additional 8 hours. Aftercooling to room temperature, the reaction mixture was poured intoacetone (4 L) and stirred for at least 15 minutes. The solution wasdecanted from the precipitated polymer. The polymer was suspended inacetone (2 L), stirred for at least 15 minutes, and allowed to settle.After decanting, the polymer was similarly washed an additional timewith acetone. The washed polymer was dried in a forced-air oven at 70°C. to afford 23.2 g.

Example 68

Copoly(diallylmethylamine/acrylamide) (50:50)

A solution of diallylmethylammonium chloride was prepared by addingdiallylmethylamine (250 g) dropwise to a solution that was cooled in anice-water bath to 10° C., of deionized water (192.3 g) and concentratedHCl (222.2 g). A solution of diallylmethylammonium chloride (59.1 g ofthe 50 percent aqueous solution), acrylamide (14.2 g), and2,2′-azobis(2-amidinopropane)dihydrochloride (2.7 g of a 20 percentaqueous solution) in deionized water (14.2 g) was heated to 60° C. for18 hours under a nitrogen atmosphere. After cooling to room temperature,the reaction solution was transferred to a Spectra/Por 1 dialysismembrane bag (molecular weight cutoff 6000 to 8000) and dialyzed againstdeionized water for at least 18 hours. The dialyzed polymer solution wasdried in a forced-air oven at 70° C. to afford 25.2 g.

Example 69

Copoly(diallyldimethylammonium chloride/acrylamide) (50:50)

A solution of diallyldimethylammonium chloride (49.8 g of a 65 percentsolution in water), acrylamide (14.2 g), and2,2′-azobis(2-amidinopropane)dihydrochloride (2.7 g of a 20 percentaqueous solution) in deionized water (91.1 g) was heated to 60° C. for18 hours under a nitrogen atmosphere. After cooling to room temperature,the reaction solution was transferred to a Spectra/Por 1 dialysismembrane bag (molecular weight cutoff 6000 to 8000) and dialyzed againstdeionized water for at least 18 hours. The dialyzed polymer solution wasdried in a forced-air oven at 70° C. to afford 27.8 g.

Example 70

Functionalization of polydiallylmethylamine with epichlorohydrin

To a solution of polydiallylmethylammonium hydrochloride (67.8 g of a44.22 percent aqueous solution), deionized water (82.8 g), and NaOH (8.7g of a 50 percent aqueous solution) was added epichlorohydrin (0.159mL). The reaction was heated under a nitrogen atmosphere at 45° C.overnight. After 30 minutes of heating, the solution gelled. After theheating period, the reaction was allowed to cool to room temperature,and concentrated HCl (10.9 g) and deionized water (250 mL) were added.The resulting slurry was transferred to a Spectra/Por 1 dialysismembrane bag (molecular weight cutoff 6000 to 8000) and dialyzed againstdeionized water for at least 18 hours. The dialyzed polymer solution wasdried in a forced-air oven at 70° C. to afford 26.8 g.

Example 71

Copoly(diallyldimethylammonium chloride/poly(ethylene glycol)methylether acrylate)

A solution of diallyldimethylammonium chloride (41.5 g of a 65 percentsolution in water), poly(ethylene glycol)methyl ether acrylate (3.0 g,Average Mn 454, obtained from Aldrich Chemical Co.), and2,2′-azobis(2-amidinopropane)dihydrochloride (0.3 g) in2-methyl-2-propanol (60 g) and deionized water (60 g) was heated to 60°C. for 16.5 hours under a nitrogen atmosphere. After cooling to roomtemperature, the reaction solution was poured into isopropanol (2 L) andstirred for at least 15 minutes. The solution was decanted from theprecipitated polymer. The polymer was suspended in isopropanol (2 L),stirred for at least 15 minutes, and allowed to settle. After decanting,the polymer was suspended in isopropanol (2 L), stirred for at least 15minutes, and allowed to settle. The washed polymer was dried in aforced-air oven at 70° C. to afford 16.3 g.

Example 72

Copoly(diallyldimethylammonium chloride/poly(propylene glycol)methylether acrylate)

A solution of diallyldimethylammonium chloride (41.5 g of a 65 percentsolution in water), poly(propylene glycol)methyl ether acrylate (3.0 g,Average Mn 202, obtained from Aldrich Chemical Co.), and2,2′-azobis(2-amidinopropane)dihydrochloride (0.3 g) in2-methyl-2-propanol (60 g) and deionized water (60 g) was heated to 60°C. for 16.5 hours under a nitrogen atmosphere. After cooling to roomtemperature, the reaction solution was poured into isopropanol (2 L) andstirred for at least 15 minutes. The solution was decanted from theprecipitated polymer. The polymer was suspended in isopropanol (2 L),stirred for at least 15 minutes, and allowed to settle. After decanting,the polymer was suspended in isopropanol (2 L), stirred for at least 15minutes, and allowed to settle. The washed polymer was dried in aforced-air oven at 70° C. to afford 18.2 g.

Example 73

Copoly(diallyldimethylammonium chloride/vinyl alcohol) (50:50)

A solution of diallyldimethylammonium chloride (32.6 g of a 65 percentsolution in water), vinyl acetate (10.53 g), and2,2′-azobis(2-amidinopropane)dihydrochloride (0.64 g) in2-methyl-2-propanol (60 g) and deionized water (60 g) was heated to 60°C. for 21 hours under a nitrogen atmosphere. After cooling to roomtemperature, the reaction solution was poured into isopropanol (2 L) andstirred for at least 15 minutes. The solution was decanted from theprecipitated polymer. The polymer was suspended in isopropanol (2 L),stirred for at least 15 minutes, and allowed to settle. After decanting,the polymer was suspended in isopropanol (2 L), stirred for at least 15minutes, and allowed to settle. The washed polymer was dried in aforced-air oven at 70° C. to afford 11.5 g. To a solution of a portionof the washed polymer (5.5 g) in deionized water (100 mL) was added NaOH(0.15 g of a 50 percent aqueous solution). The solution was heated at60° C. with stirring for 23.5 hours. The reaction solution wastransferred to a Spectra/Por 1 dialysis membrane bag (molecular weightcutoff 6000 to 8000) and dialyzed against deionized water for at least18 hours. The dialyzed polymer solution was dried in a forced-air ovenat 70° C. to afford 4.5 g.

Example 74

Copoly(diallyldimethylammonium chloride/poly(ethylene glycol acrylate)

A solution of diallyldimethylammonium chloride (36.9 g of a 65 percentsolution in water), poly(ethylene glycol)methyl ether acrylate (6.0 g,Average Mn 375, obtained from Aldrich Chemical Co.), and2,2′-azobis(2-amidinopropane)dihydrochloride (0.3 g) in deionized water(120 g) was heated to 60° C. for 18 hours under a nitrogen atmosphere.After cooling to room temperature, the reaction solution was poured intoacetone (2 L) and stirred for at least 15 minutes. The solution wasdecanted from the precipitated polymer. The polymer was suspended inacetone (2 L), stirred for at least 15 minutes, and allowed to settle.After decanting, the polymer was suspended in acetone (2 L), stirred forat least 15 minutes, and allowed to settle. The washed polymer was driedin a forced-air oven at 70° C. to afford 20.0 g.

Example 75

Copoly(diallyldimethylammonium chloride/acrylic acid) (90:10)

A solution of diallyldimethylammonium chloride (73.29 g of a 65 percentsolution in water), acrylic acid (2.36 g) and2,2′-azobis(2-amidinopropane)dihydrochloride (0.444 g) in deionizedwater (175 mL) was heated to 60° C. for 18 hours under a nitrogenatmosphere. After cooling to room temperature, the reaction solution waspoured into isopropanol (2 L) and stirred for at least 15 minutes. Thesolution was decanted from the precipitated polymer. The polymer wassuspended in isopropanol (2 L), stirred for at least 15 minutes, andallowed to settle. After decanting, the polymer was suspended inisopropanol (2 L), ground in a blender for at least 5 minutes, stirredfor at least 15 minutes, and allowed to settle. The washed polymer wasdried in a forced-air oven at 70° C. to afford 35.0 g.

Example 76

Copoly(diallyldimethylammonium chloride/acrylic acid) (75:25)

A solution of diallyldimethylammonium chloride (66.97 g of a 65 percentsolution in water), acrylic acid (6.47 g) and2,2′-azobis(2-amidinopropane)dihydrochloride (0.487 g) in deionizedwater (175 mL) was heated to 60° C. for 18 hours under a nitrogenatmosphere. After cooling to room temperature, the reaction solution waspoured into isopropanol (2 L) and stirred for at least 15 minutes. Thesolution was decanted from the precipitated polymer. The polymer wassuspended in isopropanol (2 L), stirred for at least 15 minutes, andallowed to settle. After decanting, the polymer was suspended inisopropanol (2 L), ground in a blender for at least 5 minutes, stirredfor at least 15 minutes, and allowed to settle. The washed polymer wasdried in a forced-air oven at 70° C. to afford 38.9 g.

Example 77

Functionalization of poly(diallylmethylamine) with 3-bromopropionic acid

A basic solution of polydiallylmethylamine was prepared by mixingpolydiallylmethylamine hydrochloride (615.4 g of a 44.22 percent aqueoussolution), deionized water (745.2 g) and NaOH (78.0 g of a 50 percentaqueous solution) overnight.

To a portion of the basic solution of polydiallylmethylamine (158.6 g)was added deionized water (141.4 g) and 3-bromopropionic acid (15.5 g).This solution was heated to 50° C., and then NaOH (16.2 g of a 50percent aqueous solution) was added. The reaction solution was heated at50° C. for 18.5 hours. After cooling to room temperature, the reactionsolution was transferred to a Spectra/Por 1 dialysis membrane bag(molecular weight cutoff 6000 to 8000) and dialyzed against deionizedwater for at least 18 hours. The dialyzed polymer solution was dried ina forced-air oven at 70° C. to afford 29.2 g.

Example 78

Functionalization of poly(diallylmethylamine) with 4-bromobutyric acid

To a portion of the basic solution of polydiallylmethylamine (158.6 g;Example 77) was added deionized water (141.4 g) and 3-bromobutyric acid(17.0 g). This solution was heated to 50° C., and then NaOH (16.2 g of a50 percent aqueous solution) was added. The reaction solution was heatedat 50° C. for 18.5 hours. After cooling to room temperature, thereaction solution was transferred to a Spectra/Por 1 dialysis membranebag (molecular weight cutoff 6000 to 8000) and dialyzed againstdeionized water for at least 18 hours. The dialyzed polymer solution wasdried in a forced-air oven at 70° C. to afford 20.0 g.

Example 79

Functionalization of poly(diallylmethylamine) with 2-bromoethanesulfonicacid

To a portion of the basic solution of polydiallylmethylamine (158.6 g;Example 77) was added deionized water (141.4 g) and2-bromoethanesulfonic acid (21.4 g). This solution was heated to 50° C.,and then NaOH (16.2 g of a 50 percent aqueous solution) was added. Thereaction solution was heated at 50° C. for 19 hours. After cooling toroom temperature, the reaction solution was transferred to a Spectra/Por1 dialysis membrane bag (molecular weight cutoff 6000 to 8000) anddialyzed against deionized water for at least 18 hours. The dialyzedpolymer solution was dried in a forced-air oven at 70° C. to afford 28:8g.

Example 80

Functionalization of poly(diallylmethylamine) with 1,3-propane sultone

To a portion of the basic solution of polydiallylmethylamine (158.6 g;Example 77) was added deionized water (141.4 g) and 1,3-propane sultone(12.4 g). This solution was heated to 50° C., and then NaOH (16.2 g of a50 percent aqueous solution) was added. The reaction solution was heatedat 50° C. for 19 hours. After cooling to room temperature, the reactionsolution was poured into isopropanol (2 L) and stirred for at least 15minutes. The solution was decanted from the precipitated polymer. Thepolymer was suspended in isopropanol (2 L), stirred for at least 15minutes, and allowed to settle. After decanting, the polymer wassuspended in isopropanol (2 L), ground in a blender for at least 5minutes, stirred for at least 15 minutes, and allowed to settle. Thewashed polymer was dried in a forced-air oven at 70° C. to afford 38.8g.

Example 81

Functionalization of poly(diallylmethylamine) with 2-bromoethanol

To a portion of the basic solution of polydiallylmethylamine (158.6 g;Example 77) was added deionized water (150 mL) and 2-bromoethanol (40.06g). This solution was heated to 45° C., and then NaOH (16.2 g of a 50percent aqueous solution) was added. The reaction solution was heated at45° C. for 21 hours. After cooling to room temperature, the reactionsolution was transferred to a Spectra/Por 1 dialysis membrane bag(molecular weight cutoff 6000 to 8000) and dialyzed against deionizedwater for at least 18 hours. The dialyzed polymer solution was dried ina forced-air oven at 70° C. to afford 40.2 g.

Example 82

Functionalization of poly(diallylamine) with 2-bromoethanol

A basic solution of polydiallylamine was prepared by mixingpolydiallylamine hydrochloride (519.03 g of a 28.9 percent aqueoussolution), deionized water (230.97 g) and NaOH (48.0 g of a 50 percentaqueous solution) overnight.

To a portion of the polydiallylamine basic solution (133.62 g) was added2-bromoethanol (65.77 g). This solution was heated to 45° C., and thenNaOH (16.2 g of a 50 percent aqueous solution) was added. The reactionsolution was heated at 45° C. for 18 hours. After 3 hours at 45° C.,NaOH (50 percent aqueous solution) was added to bring the pH from 8.5 to9.6. After cooling to room temperature, the reaction solution wastransferred to a Spectra/Por 1 dialysis membrane bag (molecular weightcutoff 6000 to 8000) and dialyzed against deionized water for at least18 hours. The dialyzed polymer solution was dried in a forced-air ovenat 70° C. to afford 41.0 g.

Example 83

Copoly[(3-acrylamidopropyl)trimethylammonium chloride]/acrylicacid](90:10)

A solution of (3-acrylamidopropyl)trimethylammonium chloride (64.2 g ofa 75 percent solution in water), acrylic acid (1.86 g) and2,2′-azobis(2-amidinopropane)dihydrochloride (0.351 g) in deionizedwater (190 mL) was heated to 60° C. for 8 hours under a nitrogenatmosphere. After cooling to room temperature, the reaction solution waspoured into isopropanol (2 L) and stirred for at least 15 minutes. Thesolution was decanted from the precipitated polymer. The polymer wassuspended in isopropanol (2 L), stirred for at least 15 minutes, andallowed to settle. After decanting, the polymer was suspended inisopropanol (2 L), stirred for at least 15 minutes, and allowed tosettle. The washed polymer was dried in a forced-air oven at 70° C. toafford 44.8 g.

Example 84

Copoly[(3-acrylamidopropyl)trimethylammonium chloride]/acrylicacid](75:25)

A solution of (3-acrylamidopropyl)trimethylammonium chloride (59.7 g ofa 75 percent solution in water), acrylic acid (5.21 g) and2,2′-azobis(2-amidinopropane)dihydrochloride (0.392 g) in deionizedwater (190 mL) was heated to 60° C. for 8 hours under a nitrogenatmosphere. After cooling to room temperature, the reaction solution waspoured into isopropanol (2 L) and stirred for at least 15 minutes. Thesolution was decanted from the precipitated polymer. The polymer wassuspended in isopropanol (2 L), stirred for at least 15 minutes, andallowed to settle. After decanting, the polymer was suspended inisopropanol (2 L), stirred for at least 15 minutes, and allowed tosettle. The washed polymer was dried in a forced-air oven at 70° C. toafford 47.1 g.

Example 85

Copoly(diallyldimethylammonium chloride/poly(ethylene glycol)methylether acrylate)

A solution of diallyldimethylammonium chloride (50.0 g of a 50 percentsolution in water), poly(ethylene glycol)methyl ether acrylate (25.0 g,Average Mn 454, obtained from Aldrich Chemical Co.), and2,2′-azobis(2-amidinopropane)dihydrochloride (0.5 g) in deionized water(190 mL) was heated to 60° C. for 16 hours under a nitrogen atmosphere.After cooling to room temperature, deionized water (200 mL) was addedand after thoroughly mixing, the reaction solution was transferred to aSpectra/Por 1 dialysis membrane bag (molecular weight cutoff 6000 to8000) and dialyzed against deionized water for at least 18 hours. Thedialyzed polymer solution was dried in a forced-air oven at 70° C. toafford 31.0 g.

Example 86

Copoly[(3-acrylamidopropyl)trimethylammonium chloride/poly(ethyleneglycol)methyl ether acrylate]

A solution of poly(ethylene glycol)methyl ether (10.0 g, Average Mn2,000, obtained from Aldrich Chemical Co.), triethylamine (5.06 g), and3,5-di-tert-butyl-4-hydroxyanisole (0.06 g) in tetrahydrofuran (250 mL)was cooled in an ice-water bath. While maintaining the temperature ofthe reaction solution at 5-15° C., a solution of acryloyl chloride (4.53g) in tetrahydrofuran (30 mL) was added slowly. Following the addition,the reaction solution was heated at 40° C. for 24 hours and then storedat 4° C. for 72 hours. The upper liquid layer was decanted from theprecipitate, and concentrated on a rotary evaporator to remove most ofthe tetrahydrofuran. The concentrated solution was then poured intodiethyl ether, and the light yellow precipitate was filtered and driedunder vacuum to afford 2.5 g of solid poly(ethylene glycol)methyl etheracrylate. Additional material was isolated from the initial precipitateby mixing it with tetrahydrofuran (250 mL) and heating at 35° C. for 2hours. The mixture was filtered through celite, and the filteredsolution was concentrated on a rotary evaporator to remove most of thetetrahydrofuran. The concentrated solution was poured into diethylether, and the light yellow precipitate was filtered and dried undervacuum to afford 3.2 g of solid poly(ethylene glycol) methyl etheracrylate.

A solution of (3-acrylamidopropyl)trimethylammonium chloride (18.0 g ofa 75 percent solution in water), poly(ethylene glycol)methyl etheracrylate (1.5 g), and 2,2′-azobis(2-amidinopropane)dihydrochloride (0.15g) in deionized water (60.0 g) was heated to 60° C. for 4 hours under anitrogen atmosphere. After cooling to room temperature, the reactionsolution was poured into isopropanol (2 L) and stirred for at least 15minutes. The solution was decanted from the precipitated polymer. Thepolymer was suspended in isopropanol (2 L), stirred for at least 15minutes, and allowed to settle. After decanting, the polymer wassuspended in isopropanol (2 L), stirred for at least 15 minutes, andallowed to settle. The washed polymer was dried in a forced-air oven at70° C. to afford 14.5 g.

Example 87

Preparation of a copolymer of diallyamine HCL (50% and acylamide (50%)

Diallylamine (60 g, 617 mmole) was suspended in water (200 mL) which wasacidified with concentrated HCl to pH 1.5 at 10-15 C. Acrylamide (43.85g, 617 mmol) was added and the reaction mixture was purged with nitrogenfor 10 minutes, followed by the addition of 2,2′-azobisisobutyronitrile(500 mg). The reaction mixture was slowly heated to 65 C. and theheating was continued for 16 hours under nitrogen. The reaction contentswere poured into isopropanol (2 L) and the polymer precipitated. Thesupernatant was removed and replaced with fresh isopropanol (2 L). Thisprocess was repeated 2 more times. The polymer was finally collected byfiltration and the material was dried under vacuum at 45 C. The polymerwas ground, passed through an 80 mesh sieve, and dried again in a vacuumoven to yield 100 g of product.

Example 88

Preparation of a copolymer of (3-acrylamidopropyl)trimethylammoniumcholoride (75 mole %) and acrylamide (25 mole %)

A 30-L reaction vessel was charged with(3-acrylamidopropyl)trimethylammonium chloride (2481 g of 50 percentsolution, 6 moles) and acrylamide (142.16 g, 2 moles). Isopropanol (6 L)was added and the vessel was purged with nitrogen for 10 minutes priorto the addition of 2,2′-azobisisobutyronitrile (5.28g). The reactionmixture was heated to 70 C. for 21 hours under nitrogen. The reactionmixture was collected in a bucket, the supernatant was decanted, and thematerial was suspended in boiling isopropanol (3 L). The mixture wasstirred with overhead stirrer for 20 minutes. The solvent was replacedwith fresh boiling isopropanol (3 L) and the process was repeated 3 moretimes. Finally the material was suspended in isopropanol (4 L) at roomtemperature for 1 day. The polymer became slightly brittle and wasground in a blender. The polymer was collected by filtration and washedwith isopropanol (2×3 L). The polymer was dried under vacuum at 60 C.for 2 days. The polymer was ground and passed through an 80 mesh sieveto yield 1260 g of product.

Example 89

Preparation of a copolymer of (3-acrylamidopropyl)trimethylammoniumchloride (75 mole %), crylamide (20 mole %) and N-octoylacrylamide (5mole %)

A three-necked round-bottomed flask (1 L) was charged with(3-acrylamidopropyl)trimethylammonium chloride (62 g of 50 percentsolution, 150 mmol), acrylamide (2.84 g, 40 mmol), octylacrylamide (1.83g, 10 mmol) and isopropanol 160 mL. The mixture was purged with nitrogenfor 10 minutes prior to the addition of 2,2′-azobisisobutyronitrile (132mg). The reaction mixture was heated to 70 C. for 16 hours. At the endof reaction, the solvent was removed from the reaction mixture and theprecipitated polymer was poured into boiling isopropanol (1 L). Thesolvent was replaced with fresh boiling isopropanol. The process wasrepeated 3 more times. Finally, the polymer was suspended in isopropanol(1 L) at room temperature for 6 hours. The polymer was collected anddried under vacuum at 60 C. The polymer was ground and passed through an80 mesh sieve to yield 30 g of product.

Example 90

Preparation of the methylenebisacrylamide (1 mole %) Cross-linkedcopolymer of (3-acrylamidopropyl)trimethylammonium choloride (75%)),acrylamide (20 mole %) and N-dodecylacrylamide (5 mole %)

A three-necked round-bottomed flask (1 L) was charged with(3-acrylamidopropyl)trimethylammonium chloride (124 g of 50 percentsolution, 300 mmole), acrylamide (5.68 g, 80 mmole), dodecylacrylamide(4.78 g, 20 mmole) and methylenebisacrylamide (616.7 mg, 4 mmole). Water(80 mL) and ethanol 80 mL were added. The mixture was purged withnitrogen for 10 minutes prior to the addition of2,2′-azobis(2-amidinopropane)dihydrochloride (400 mg). The reactionmixture was heated to 65° C. for 16 hours. The reaction was gelledwithin 2 hours. At the end of reaction, the solvent was removed from thereaction mixture. The precipitated polymer gel was suspended in boilingisopropanol (1 L). The solvent was replaced with fresh boilingisopropanol. The process was repeated 3 more times. Finally, the polymerwas suspended in isopropanol (1 L) and ground in a blender. The polymerwas collected and dried under vacuum at 60° C. The polymer powdered,suspended in water (2.5 L), and filtered. The gel was washed with water(4×2.5 L) followed by isopropanol (3×4 L). The polymer was dried in avacuum oven to yield 60 g of product.

Example 91

Preparation ofpoly[(n-vinylimidazole-co-(1-vinyl-3-methylimidazole-co-(1-vinyl-3-dodecylimidazole)]20/75/5

To a 5 liter flask with mechanical stirrer, nitrogen purge, andtemperature controller was added: n-vinylimidazole (500 g; 5.31 moles),deionized water (250 mL), and enough HCl to make the pH=0.8(approximately 500 mL of 37 percent solution). Enough water was added tomake the reaction solution 25 percent solids and this was degassed vianitrogen purge for 1 hour. The reaction was heated to 60° C. at whichpoint was added 2,2′-azobis(2-amidinopropane)dihydrochloride (2.5 g)dissolved in ˜2 mL of water. A small exotherm of 7° C. was noted andafter 105 minutes an additional charge of2,2′-azobis(2-amidinopropane)dihydrochloride (2.5 g of) in 2 mL of waterwas added. Total heating time at 60° C. was 8 hours. After the reactionwas cooled to room temperature, the pH was adjusted to 13.2 with aqueoussodium hydroxide and the clear liquid was poured away from the gummysolid. The gummy solid was taken up in enough deionized water to make 12percent of n-vinylimidazole homopolymer.

To a 1 liter flask with mechanical stirrer and temperature controllerwas added: 300 g n-vinylimidazole homopolymer solution and enoughconcentrated HCl to make the pH=8.25. To this was added 4.768 g dodecylbromide (0.0191 moles) and the reaction mixture was heated to 80° C. for20 hours (the solution became cloudy after a few minutes). The reactionwas allowed to cool to 40° C. and dimethyl sulfate was added in 5 mLportions (0.287 moles total). NaOH (5 mL of 50 percent) was added andthe reaction mixture was allowed to stir at room temperature for 20hours (pH ˜13.5). The reaction mixture was heated to 45° C. for 3 hoursto kill any unreacted dimethyl sulfate. The pH was adjusted to 1.2 withHCl and the mixture was triterated into isopropanol. The liquid waspoured off, the polymer was re-dissolved in deionized water andre-triterated into isopropanol. The polymer was dissolved in 300 mL ofdeionized water and 125 mL of Amberlite Cl− ion exchange resin beads for4 hours. The polymer was filtered off, the beads were rinsed with waterand the polymer solution was allowed to dry in a convection oven at 60°C. to yield 51.2 g of solid.

Example 92

Preparation of poly[(diallyl dimethyl ammonium chloride)-co-(n-vinylglycine)] 70/30

To a 500-mL flask with mechanical stirrer, nitrogen purge, andtemperature controller was added: diallyldimethyl ammonium chloride(66.85 g of 65 percent solution in water, 43.45 g solids, 0.2687 moles),allylamine HCl (24.12 g of 27.16 percent solution based on allylaminecharged in water, 0.1149 moles), and deionized water (75.69 mL) to make30 percent solids (based on un-protonated monomers charged). Thereaction mixture was degassed via nitrogen purge for 1 hour and thenheated to 60° C. at which time2,2′-azobis(2-amidinopropane)dihydrochloride (0.25 g) in ˜1 mL of waterwas added. This was followed 30 minutes later with an additional chargeof 2,2′-azobis(2-amidinopropane)dihydrochloride (0.25 g in ˜1 mL ofwater). Further additional charges were made at 5 hours, 20 hours, and28 hours. At 48 hours the temperature was raised to 80° C. for 1 hourand then turned off and the reaction was allowed to cool to roomtemperature. To this polymer solution was added chloroacetic acid(10.846 g; 0.1149 moles) and the pH was adjusted to 10 with 50 percentNaOH solution in water. This mixture was heated at 40° C. for 24 hours.The heat was then turned off and the polymer was triterated intoacetone. The liquid was poured off and the polymer was re-dissolved intodeionized water, the pH adjusted to ˜2 with HCl (37 percent) andtriterated again into acetone. The polymer was dissolved into deionizedwater once more and triterated into acetone. The polymer was thendissolved into water and placed in a 60° C. convection oven to dry to55.1 g of amber glassy solid.

Example 93

Preparation of Poly[(diallyl dimethyl ammonium chloride)-co-(n-allylpentylamine)-co-(n-allyl glycine)

To a 500-mL flask with mechanical stirrer, nitrogen purge, andtemperature controller was added: diallyldimethylammonium chloride (891g of 65 percent solution in water; 579.15 g solids; 3.58 moles),allylamine HCl (321.5 g of 27.16 percent solution based on allylaminecharged in water, 1.53 moles), and deionized water (454 mL) to make 40percent solids (based on un-protonated monomers charged). The reactionmixture was degassed via nitrogen purge for 1 hour and then heated to60° C. at which time 1.67 g of2,2′-azobis(2-amidinopropane)dihydrochloride in ˜2 mL of water wasadded. This was followed 15 minutes later with an additional charge of2,2′-azobis(2-amidinopropane)dihydrochloride (1.67 g). Additionalcharges were made at 16 hours, and 24 hours. At 40 hours the temperaturewas raised to 80° C. for 1 hour and then turned off and the reaction wasallowed to cool to room temperature.

To a 500 mnL flask with mechanical stirrer and temperature controllerwas added: 250 g of the reaction mixture above (40 percent, 100 g solidsbased on un-protonated monomers charged). The pH was adjusted to 10 with50 percent NaOH in water. The temperature was raised to 70° C. and thereaction was subsequently charged with n-chlorodecane (9.32 mL; 0.046moles) and allowed to stir for 20 hours. The reaction was allowed tocool to room temperature before adding chloroacetic acid (30 g; 0.3177moles) and the pH was readjusted to 10. The reaction was allowed to stirat 40° C. for 20 hours. The polymer was then precipitated into acetoneand the liquid was decanted. The polymer was redissolved in deionizedwater and re-triterated into acetone; this procedure was repeated oncemore. The polymer was then dissolved in deionized water and the pH wasadjusted to ˜2 with HCl (37 percent) and the triteration into acetoneprocedure was repeated three more times. The polymer was dissolved inwater and placed in a convection oven at 60° C. to dry to 36.9 g ofglassy solid.

No Example 94 Example 95

Preparation of Poly[((3-acrylamidopropyl)trimethylammoniumchloride)-co-(acrylamide)-co-(n-octadecylacrylamide)] 60/35/5

To a 500-mL flask with mechanical stirrer, temperature controller, andnitrogen purge was added: (3-acrylamidopropyl)trimethylammonium chloride(25.04 g of 75 percent in water; 18.78 g solids; 0.091 moles),acrylamide (3.77 g; 0.053 moles), n-octadecylacrylamide (2.45 g; 0.0076moles), deionized water (12.52 mL), and isopropanol (121 mL). Thismixture was degassed for 1 hour prior to heating to 70° C.2,2′-Azobisisobutyronitrile (0.1 g) was added when the temperaturereached 62° C. and all of the reactants were dissolved. The reaction wasallowed to heat with stirring and nitrogen purge for 4 hours.Isopropanol (200 mL) was added to the flask and the heat was turned off.The precipitated polymer was stirred in the hot isopropanol for tenminutes before pouring off the liquid. The polymer was scraped out ofthe flask and dried in a 60° C. convection oven to yield 21.2 g ofsolid.

Example 96

Preparation of Poly[(diallyl ammonium choloride)-co-(acrylamide)] 25/75

To a 500-mL flask with mechanical stirrer, temperature controller, andnitrogen purge was added: diallylamine (8.88 g; 0.092 moles), anddeionized water (20 mL). The mixture was cooled in an ice bath and 50percent concentrated HCL in water was slowly added dropwise until the pHreached 0.86. Acrylamide (19.49 g; 0.2749 moles),2,2′-azobis(2-amidinopropane)dihydrochloride (0.31 g), and deionizedwater (20 mL) were added. The reaction mixture was degassed withnitrogen for 30 minutes and the temperature was raised to 55° C. atwhich point the flask was placed in an ice bath to control the exotherm(maximum temperature 78° C.). The temperature was maintained at 60° C.for 4 hours. The polymer was precipitated into acetone and washed twicewith more acetone. The polymer was dried in a 70° C. convection oven toyield 25.1 g of solid.

Example 97

Preparation of Poly[(diallyl ammonium chloride)-co-(acrylamide)] 75/25

To a 500-mL flask with mechanical stirrer, temperature controller, andnitrogen purge was added: diallylamine (20.69 g; 0.213 moles), anddeionized water (20 mL). The mixture was cooled in an ice bath and 50percent concentrated HCL in water was added dropwise until the pHreached 0.9. Acrylamide (5.05 g; 0.0711 moles),2,2′-azobis(2-amidinopropane)dihydrochloride (0.335 g), and deionizedwater (20 mL) were added. The reaction mixture was degassed withnitrogen for 30 minutes and the temperature was raised to 65° C. Anadditional charge of 2,2′-azobis(2-amidinopropane)dihydrochloride (0.335g) was made at 24 hours and another at 48 hours. At 72 hours the polymerwas precipitated into acetone and washed twice with more acetone. Thepolymer was dried in a 70° C. convection oven to yield 24.6 g of solid.

Example 98

Preparation of Poly[((3-acrylamidopropyl)trimethylammoniumchloride)-co-(acrylamide)-co-(n-octadecylacrylamide)] 50/45/5

To a 500-mL flask with mechanical stirrer, temperature controller, andnitrogen purge was added: (3-acrylamidopropyl)trimethylammonium chloride(22.7 g of 75 percent in water; 17.0 g solids), acrylamide (5.3 g),n-octadecylacrylamide (2.7 g), deionized water (11.4 mL), andisopropanol (132 mL). This mixture was degassed for 1 hour prior toheating to 70° C. 2,2′-Azobisisobutyronitrile (0.11 g) was added whenthe temperature reached 62° C. and all of the reactants were dissolved.The reaction was allowed to heat with stirring and nitrogen purge for 4hours. Isopropanol (200 mL) was added to the flask and the heat wasturned off. The precipitated polymer was stirred in the hot isopropanolfor ten minutes before pouring off the liquid. The polymer was scrapedout of the flask and dried in a 60° C. convection oven to yield 18.3 gof solid.

Fat-Binding Evaluation via Paper Staining

The model consists of male, Sprague Dawly rats, 160 g, housedindividually in wire mesh cages. They were acclimated to the facilityfor six days, during which time they were fed a chow based dietsupplemented with 15 percent lard by weight. Feed and water wereprovided ad lithium. The animals were then randomly assigned to groupsof four and fed test diets for three days. The test diet was also a chowbased feed. A lipase inhibitor (Orlistat) was added at 0.04 percent byweight and the polymer was added at 0.30 percent by weight. They weremixed in the feed as a powder followed by the addition of thesupplemented fat in the form of lard at 15 percent by weight. During thefinal 24 hours of the treatment period an 8.5″×11″ sheet of white paperwas placed beneath each cage. One inch squares were drawn on the papercreating a grid of 80 squares. When oil in the form of unabsorbeddietary triglyceride seeps from the stool, it stains the paper. This canbe readily discerned from urine if the papers were allowed to dry forsix hours. The oil stains confer translucence to the paper. The squaresthat contain these oil stains were counted and expressed as a percentageof total area stained. Some of the examples described above were testedin this model, and the following results were obtained:

Test Polymer Percentage of Paper Stained Control 1: 0 no lipaseinhibitor no polymer Control 2: 39 ± 6 no polymer (average of 24experiments) Example 1 9 2 17 3 8 4 9 5 7 6 10 7 7 8 13 9 11 10 11 11 1912 7 13 11 14 12 15 7 16 8 17 4 18 7 19 4 20 7 21 9 22 17 23 9 24 20 258 26 18 27 41 28 9 29 7 30 12 31 17 32 14 33 13 34 9 35 15 36 17 37 2238 18 39 28 40 4 41 19 42 no example 43 13 44 7 45 12 46 10 47 21 48 noexample 49 10 50 16 51 10 52 5 53 6 54 11 55 13 56 13 57 18 58 19 59 460 11 61 11 62 12 63 6 64 6 65 18 66 67 18 68 15 69 13 70 14 71 10 72 1573 7 74 6 75 7 76 13 77 15 78 22 79 8 80 21 81 9 82 8 83 9 84 13 85 6 8614 87 12 88 9 89 7 90 5 91 18 92 13 93 11 94 no example 95 9 96 12 97 1398 2

While this invention has been particularly shown and described withreferences to preferred embodiments thereof, it will be understood bythose skilled in the art that various changes in form and details may bemade therein without departing from the spirit and scope of theinvention as defined by the appended claims. Those skilled in the artwill recognize or be able to ascertain using no more than routineexperimentation, many equivalents to the specific embodiments of theinvention described specifically herein. Such equivalents are intendedto be encompassed in the scope of the claims.

What is claimed is:
 1. A method of treating obesity in a mammalcomprising the step of orally administering to the mammal an effectiveamount of a fat binding polymer, salt, or copolymer thereof,characterized by a repeat unit having the formula: (VIII)

in combination with at least one lipase inhibitor.
 2. The method ofclaim 1 wherein said lipase inhibitor is tetrahydrolipstatin.
 3. Themethod of claim 1 whereinPoly(N,N-di(2,3-dihydroxypropyl)allylamine)hydrochloride is orallyadministered to the mammal.
 4. A method for treating steatorrhea in amammal comprising the step of orally administering to the mammal atherapeutic amount of a polymer characterized by a repeat unit havingthe formula:


5. A method for treating hypertriglyceridemia in a mammal comprising thestep of administering to the mammal a therapeutically effective amountof at least one lipase inhibitor and a polymer characterized by acombination of repeat units having the formula:


6. A method for reducing the absorption of dietary fat in a mammalcomprising the step of orally administering to the mammal atherapeutically effective amount of at least one lipase inhibitor and apolymer characterized by a combination of repeat units having theformula:


7. A polymer, salt or copolymer thereof, characterized by a repeat unithaving the formula: